Skip to content
2000
Volume 32, Issue 15
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Metabolic syndrome (MetS) is a complex of serious pathologies with a high prevalence worldwide. Disruption of mitochondrial biogenesis and its interaction with other cell organelles plays an important role in the development of MetS. Studies have revealed the phenotypic and functional heterogeneity of mitochondria that exist within a single cell and can regulate metabolic signaling pathways, influencing the development of metabolic diseases. Excessive intake of fatty acids leads to changes in fatty acid metabolism that affect the biology of important cell organelles - the lipid droplets, whose specific biology is not fully understood. Perhaps targeted molecular genetic stimulation aimed at regulating the contact between mitochondria and lipids can break the vicious cycle of inflammation in MetS and restore normal cell function, reducing the risk of developing concomitant pathologies. The review describes potential (promising) therapeutic molecular targets associated with mitochondria and lipid droplets, focusing on the proteins involved in their contact and emphasizing their role in the pathogenesis of MetS.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673309247240610050423
2024-06-26
2025-10-30

  • From This Site

    /content/journals/cmc/10.2174/0109298673309247240610050423
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. SaklayenM.G. The global epidemic of the metabolic syndrome.Curr. Hypertens. Rep.20182021210.1007/s11906‑018‑0812‑z29480368
     [Google Scholar]
  2. HuangP.L. A comprehensive definition for metabolic syndrome.Dis. Model. Mech.200925-623123710.1242/dmm.00118019407331
     [Google Scholar]
  3. PrasunP. Mitochondrial dysfunction in metabolic syndrome.Biochim. Biophys. Acta Mol. Basis Dis.202018661016583810.1016/j.bbadis.2020.16583832428560
     [Google Scholar]
  4. ZhangS. PengX. YangS. LiX. HuangM. WeiS. LiuJ. HeG. ZhengH. YangL. LiH. FanQ. The regulation, function, and role of lipophagy, a form of selective autophagy, in metabolic disorders.Cell Death Dis.202213213210.1038/s41419‑022‑04593‑335136038
     [Google Scholar]
  5. EjarqueM. Ceperuelo-MallafréV. SerenaC. Maymo-MasipE. DuranX. Díaz-RamosA. Millan-ScheidingM. Núñez-ÁlvarezY. Núñez-RoaC. GamaP. Garcia-RovesP.M. PeinadoM.A. GimbleJ.M. ZorzanoA. VendrellJ. Fernández-VeledoS. Adipose tissue mitochondrial dysfunction in human obesity is linked to a specific DNA methylation signature in adipose-derived stem cells.Int. J. Obes.20194361256126810.1038/s41366‑018‑0219‑630262812
     [Google Scholar]
  6. ZhengY. YangN. PangY. GongY. YangH. DingW. YangH. Mitochondria-associated regulation in adipose tissues and potential reagents for obesity intervention.Front. Endocrinol.202314113234210.3389/fendo.2023.113234237396170
     [Google Scholar]
  7. SpinelliJ.B. HaigisM.C. The multifaceted contributions of mitochondria to cellular metabolism.Nat. Cell Biol.201820774575410.1038/s41556‑018‑0124‑129950572
     [Google Scholar]
  8. RossmannM.P. DuboisS.M. AgarwalS. ZonL.I. Mitochondrial function in development and disease.Dis. Model. Mech.2021146dmm04891210.1242/dmm.04891234114603
     [Google Scholar]
  9. AkbariM. KirkwoodT.B.L. BohrV.A. Mitochondria in the signaling pathways that control longevity and health span.Ageing Res. Rev.20195410094010.1016/j.arr.2019.10094031415807
     [Google Scholar]
  10. BoudinaS. GrahamT.E. Mitochondrial function/dysfunction in white adipose tissue.Exp. Physiol.20149991168117810.1113/expphysiol.2014.08141425128326
     [Google Scholar]
  11. BenadorI.Y. VeliovaM. MahdavianiK. PetcherskiA. WikstromJ.D. AssaliE.A. Acín-PérezR. ShumM. OliveiraM.F. CintiS. SztalrydC. BarshopW.D. WohlschlegelJ.A. CorkeyB.E. LiesaM. ShirihaiO.S. Mitochondria bound to lipid droplets have unique bioenergetics, composition, and dynamics that support lipid droplet expansion.Cell Metab.2018274869885.e610.1016/j.cmet.2018.03.00329617645
     [Google Scholar]
  12. SzabadkaiG. SimoniA.M. ChamiM. WieckowskiM.R. YouleR.J. RizzutoR. Drp-1-dependent division of the mitochondrial network blocks intraorganellar Ca2+ waves and protects against Ca2+-mediated apoptosis.Mol. Cell2004161596810.1016/j.molcel.2004.09.02615469822
     [Google Scholar]
  13. FriedenM. JamesD. CastelbouC. DanckaertA. MartinouJ.C. DemaurexN. Ca(2+) homeostasis during mitochondrial fragmentation and perinuclear clustering induced by hFis1.J. Biol. Chem.200427921227042271410.1074/jbc.M31236620015024001
     [Google Scholar]
  14. NgoJ. OstoC. VillalobosF. ShirihaiO.S. Mitochondrial heterogeneity in metabolic diseases.Biology202110992710.3390/biology1009092734571805
     [Google Scholar]
  15. BellerM. HerkerE. FüllekrugJ. Grease on-Perspectives in lipid droplet biology.Semin. Cell Dev. Biol.20201089410110.1016/j.semcdb.2020.06.01732636101
     [Google Scholar]
  16. Fader KaiserC.M. RomanoP.S. VanrellM.C. PocognoniC.A. JacobJ. CarusoB. DelguiL.R. Biogenesis and breakdown of lipid droplets in pathological conditions.Front. Cell Dev. Biol.2022982624810.3389/fcell.2021.82624835198567
     [Google Scholar]
  17. SchuldinerM. BohnertM. A different kind of love – lipid droplet contact sites.Biochim. Biophys. Acta Mol. Cell Biol. Lipids201718621010 Pt B1188119610.1016/j.bbalip.2017.06.00528627434
     [Google Scholar]
  18. CuiL. LiuP. Two types of contact between lipid droplets and mitochondria.Front. Cell Dev. Biol.2020861832210.3389/fcell.2020.61832233385001
     [Google Scholar]
  19. SafiR. Sánchez-ÁlvarezM. BoschM. DemangelC. PartonR.G. PolA. Defensive-lipid droplets: Cellular organelles designed for antimicrobial immunity.Immunol. Rev.2023317111313610.1111/imr.1319936960679
     [Google Scholar]
  20. WelteM.A. GouldA.P. Lipid droplet functions beyond energy storage.Biochim. Biophys. Acta Mol. Cell Biol. Lipids201718621010 Pt B1260127210.1016/j.bbalip.2017.07.00628735096
     [Google Scholar]
  21. BoschM. Sánchez-ÁlvarezM. FajardoA. KapetanovicR. SteinerB. DutraF. MoreiraL. LópezJ.A. CampoR. MaríM. Morales-PaytuvíF. TortO. GubernA. TemplinR.M. CursonJ.E.B. MartelN. CatalàC. LozanoF. TebarF. EnrichC. VázquezJ. Del PozoM.A. SweetM.J. BozzaP.T. GrossS.P. PartonR.G. PolA. Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense.Science20203706514eaay808510.1126/science.aay808533060333
     [Google Scholar]
  22. BersukerK. OlzmannJ.A. Establishing the lipid droplet proteome: Mechanisms of lipid droplet protein targeting and degradation.Biochim. Biophys. Acta Mol. Cell Biol. Lipids201718621010 Pt B1166117710.1016/j.bbalip.2017.06.00628627435
     [Google Scholar]
  23. ThiamA.R. BellerM. The why, when and how of lipid droplet diversity.J. Cell Sci.20171302jcs.19202110.1242/jcs.19202128049719
     [Google Scholar]
  24. WangH. AirolaM.V. ReueK. How lipid droplets “TAG” along: Glycerolipid synthetic enzymes and lipid storage.Biochim. Biophys. Acta Mol. Cell Biol. Lipids20171862101131114510.1016/j.bbalip.2017.06.01028642195
     [Google Scholar]
  25. LiuP. BartzR. ZehmerJ.K. YingY. ZhuM. SerreroG. AndersonR.G.W. Rab-regulated interaction of early endosomes with lipid droplets.Biochim. Biophys. Acta Mol. Cell Res.20071773678479310.1016/j.bbamcr.2007.02.00417395284
     [Google Scholar]
  26. PuJ. HaC.W. ZhangS. JungJ.P. HuhW.K. LiuP. Interactomic study on interaction between lipid droplets and mitochondria.Protein Cell20112648749610.1007/s13238‑011‑1061‑y21748599
     [Google Scholar]
  27. OzekiS. ChengJ. Tauchi-SatoK. HatanoN. TaniguchiH. FujimotoT. Rab18 localizes to lipid droplets and induces their close apposition to the endoplasmic reticulum-derived membrane.J. Cell Sci.2005118122601261110.1242/jcs.0240115914536
     [Google Scholar]
  28. BinnsD. JanuszewskiT. ChenY. HillJ. MarkinV.S. ZhaoY. GilpinC. ChapmanK.D. AndersonR.G.W. GoodmanJ.M. An intimate collaboration between peroxisomes and lipid bodies.J. Cell Biol.2006173571973110.1083/jcb.20051112516735577
     [Google Scholar]
  29. OlzmannJ.A. CarvalhoP. Dynamics and functions of lipid droplets.Nat. Rev. Mol. Cell Biol.201920313715510.1038/s41580‑018‑0085‑z30523332
     [Google Scholar]
  30. ShulmanG.I. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease.N. Engl. J. Med.2014371121131114110.1056/NEJMra101103525229917
     [Google Scholar]
  31. XuS. ZhangX. LiuP. Lipid droplet proteins and metabolic diseases.Biochim. Biophys. Acta Mol. Basis Dis.2018186455 Pt B1968198310.1016/j.bbadis.2017.07.01928739173
     [Google Scholar]
  32. ZadoorianA. DuX. YangH. Lipid droplet biogenesis and functions in health and disease.Nat. Rev. Endocrinol.202319844345910.1038/s41574‑023‑00845‑037221402
     [Google Scholar]
  33. ParryH.A. GlancyB. Energy transfer between the mitochondrial network and lipid droplets in insulin resistant skeletal muscle.Curr. Opin. Physiol.20212410048710.1016/j.cophys.2022.10048735274067
     [Google Scholar]
  34. HouzelleA. JörgensenJ.A. SchaartG. DaemenS. van PolanenN. FealyC.E. HesselinkM.K.C. SchrauwenP. HoeksJ. Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity.Diabetologia202164242443610.1007/s00125‑020‑05335‑w33258025
     [Google Scholar]
  35. RuegseggerG.N. CreoA.L. CortesT.M. DasariS. NairK.S. Altered mitochondrial function in insulin-deficient and insulin-resistant states.J. Clin. Invest.201812893671368110.1172/JCI12084330168804
     [Google Scholar]
  36. de AlmeidaM.E. ØrtenbladN. PetersenM.H. SchjerningA.S.N. WentorfE.K. JensenK. HøjlundK. NielsenJ. Acute exercise increases the contact between lipid droplets and mitochondria independently of obesity and type 2 diabetes.J. Physiol.2023601101797181510.1113/JP28438637013398
     [Google Scholar]
  37. KodihaM. FlamantE. WangY.M. StochajU. Defining the short-term effects of pharmacological 5′-AMP activated kinase modulators on mitochondrial polarization, morphology and heterogeneity.PeerJ20186e546910.7717/peerj.546930186684
     [Google Scholar]
  38. AryamanJ. JohnstonI.G. JonesN.S. Mitochondrial Heterogeneity.Front. Genet.2019971810.3389/fgene.2018.0071830740126
     [Google Scholar]
  39. DzejaP.P. BortolonR. Perez-TerzicC. HolmuhamedovE.L. TerzicA. Energetic communication between mitochondria and nucleus directed by catalyzed phosphotransfer.Proc. Natl. Acad. Sci. USA20029915101561016110.1073/pnas.15225999912119406
     [Google Scholar]
  40. ZorovD.B. JuhaszovaM. SollottS.J. Mitochondrial ROS-induced ROS release: An update and review.Biochim. Biophys. Acta Bioenerg.200617575-650951710.1016/j.bbabio.2006.04.02916829228
     [Google Scholar]
  41. Al-MehdiA.B. PastukhV.M. SwigerB.M. ReedD.J. PatelM.R. BardwellG.C. PastukhV.V. AlexeyevM.F. GillespieM.N. Perinuclear mitochondrial clustering creates an oxidant-rich nuclear domain required for hypoxia-induced transcription.Sci. Signal.20125231ra4710.1126/scisignal.200271222763339
     [Google Scholar]
  42. RizzutoR. PintonP. CarringtonW. FayF.S. FogartyK.E. LifshitzL.M. TuftR.A. PozzanT. Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses.Science199828053701763176610.1126/science.280.5370.17639624056
     [Google Scholar]
  43. KannO. KovácsR. Mitochondria and neuronal activity.Am. J. Physiol. Cell Physiol.20072922C641C65710.1152/ajpcell.00222.200617092996
     [Google Scholar]
  44. ArzuaT. YanY. LiuX. DashR.K. LiuQ.S. BaiX. Synaptic and mitochondrial mechanisms behind alcohol-induced imbalance of excitatory/inhibitory synaptic activity and associated cognitive and behavioral abnormalities.Transl. Psychiatry20241415110.1038/s41398‑024‑02748‑838253552
     [Google Scholar]
  45. HollanderJ.M. ThapaD. ShepherdD.L. Physiological and structural differences in spatially distinct subpopulations of cardiac mitochondria: influence of cardiac pathologies.Am. J. Physiol. Heart Circ. Physiol.20143071H1H1410.1152/ajpheart.00747.201324778166
     [Google Scholar]
  46. DabkowskiE.R. WilliamsonC.L. BukowskiV.C. ChapmanR.S. LeonardS.S. PeerC.J. CalleryP.S. HollanderJ.M. Diabetic cardiomyopathy-associated dysfunction in spatially distinct mitochondrial subpopulations.Am. J. Physiol. Heart Circ. Physiol.20092962H359H36910.1152/ajpheart.00467.200819060128
     [Google Scholar]
  47. YuJ. ZhangS. CuiL. WangW. NaH. ZhuX. LiL. XuG. YangF. ChristianM. LiuP. Lipid droplet remodeling and interaction with mitochondria in mouse brown adipose tissue during cold treatment.Biochim. Biophys. Acta Mol. Cell Res.20151853591892810.1016/j.bbamcr.2015.01.02025655664
     [Google Scholar]
  48. RamboldA.S. CohenS. Lippincott-SchwartzJ. Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy, and mitochondrial fusion dynamics.Dev. Cell201532667869210.1016/j.devcel.2015.01.02925752962
     [Google Scholar]
  49. NguyenT.B. LouieS.M. DanieleJ.R. TranQ. DillinA. ZoncuR. NomuraD.K. OlzmannJ.A. DGAT1-dependent lipid droplet biogenesis protects mitochondrial function during starvation-induced autophagy.Dev. Cell2017421921.e510.1016/j.devcel.2017.06.00328697336
     [Google Scholar]
  50. Gordaliza-AlagueroI. CantóC. ZorzanoA. Metabolic implications of organelle-mitochondria communication.EMBO Rep.2019209e4792810.15252/embr.20194792831418169
     [Google Scholar]
  51. TwigG. ElorzaA. MolinaA.J.A. MohamedH. WikstromJ.D. WalzerG. StilesL. HaighS.E. KatzS. LasG. AlroyJ. WuM. PyB.F. YuanJ. DeeneyJ.T. CorkeyB.E. ShirihaiO.S. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy.EMBO J.200827243344610.1038/sj.emboj.760196318200046
     [Google Scholar]
  52. FreyreC.A.C. RauherP.C. EjsingC.S. KlemmR.W. MIGA2 links mitochondria, the ER, and lipid droplets and promotes De Novo lipogenesis in adipocytes.Mol. Cell2019765811825.e1410.1016/j.molcel.2019.09.01131628041
     [Google Scholar]
  53. HermsA. BoschM. ReddyB.J.N. SchieberN.L. FajardoA. RupérezC. Fernández-VidalA. FergusonC. RenteroC. TebarF. EnrichC. PartonR.G. GrossS.P. PolA. AMPK activation promotes lipid droplet dispersion on detyrosinated microtubules to increase mitochondrial fatty acid oxidation.Nat. Commun.201561717610.1038/ncomms817626013497
     [Google Scholar]
  54. CuiL. MirzaA.H. ZhangS. LiangB. LiuP. Lipid droplets and mitochondria are anchored during brown adipocyte differentiation.Protein Cell2019101292192610.1007/s13238‑019‑00661‑131667701
     [Google Scholar]
  55. AlbersP.H. PedersenA.J.T. BirkJ.B. KristensenD.E. VindB.F. BabaO. NøhrJ. HøjlundK. WojtaszewskiJ.F.P. Human muscle fiber type-specific insulin signaling: impact of obesity and type 2 diabetes.Diabetes201564248549710.2337/db14‑059025187364
     [Google Scholar]
  56. ShawC.S. JonesD.A. WagenmakersA.J.M. Network distribution of mitochondria and lipid droplets in human muscle fibres.Histochem. Cell Biol.20081291657210.1007/s00418‑007‑0349‑817938948
     [Google Scholar]
  57. KahnD. PerreaultL. MaciasE. ZariniS. NewsomS.A. StraussA. KeregeA. HarrisonK. Snell-BergeonJ. BergmanB.C. Subcellular localisation and composition of intramuscular triacylglycerol influence insulin sensitivity in humans.Diabetologia202164116818010.1007/s00125‑020‑05315‑033128577
     [Google Scholar]
  58. PerreaultL NewsomSA StraussA. Intracellular localization of diacylglycerols and sphingolipids influences insulin sensitivity and mitochondrial function in human skeletal muscle.JCI Insight.201833e968010.1172/jci.insight.96805
     [Google Scholar]
  59. GuyardV. Monteiro-CardosoV.F. OmraneM. SauvanetC. HoucineA. BoulogneC. Ben MbarekK. VitaleN. FaklarisO. El KhalloukiN. ThiamA.R. GiordanoF. ORP5 and ORP8 orchestrate lipid droplet biogenesis and maintenance at ER–mitochondria contact sites.J. Cell Biol.20222219e20211210710.1083/jcb.20211210735969857
     [Google Scholar]
  60. YangM. LuoS. YangJ. ChenW. HeL. LiuD. ZhaoL. WangX. Lipid droplet - mitochondria coupling: A novel lipid metabolism regulatory hub in diabetic nephropathy.Front. Endocrinol. (Lausanne)202213101738710.3389/fendo.2022.101738736387849
     [Google Scholar]
  61. SymondsM.E. FarhatG. AldissP. PopeM. BudgeH. Brown adipose tissue and glucose homeostasis – the link between climate change and the global rise in obesity and diabetes.Adipocyte201981465010.1080/21623945.2018.155168930463471
     [Google Scholar]
  62. NgoJ. BenadorI.Y. BrownsteinA.J. VergnesL. VeliovaM. ShumM. Acín-PérezR. ReueK. ShirihaiO.S. LiesaM. Isolation and functional analysis of peridroplet mitochondria from murine brown adipose tissue.STAR Protocols20212110024310.1016/j.xpro.2020.10024333458705
     [Google Scholar]
  63. MillerN. WolfD. AlsabeehN. MahdavianiK. SegawaM. LiesaM. ShirihaiO.S. High-throughput image analysis of lipid-droplet-bound mitochondria.Methods Mol. Biol.2021227628530310.1007/978‑1‑0716‑1266‑8_2234060050
     [Google Scholar]
  64. VeliovaM. PetcherskiA. LiesaM. ShirihaiO.S. The biology of lipid droplet-bound mitochondria.Semin. Cell Dev. Biol.2020108556410.1016/j.semcdb.2020.04.01332446655
     [Google Scholar]
  65. BenadorI.Y. VeliovaM. LiesaM. ShirihaiO.S. Mitochondria bound to lipid droplets: where mitochondrial dynamics regulate lipid storage and utilization.Cell Metab.201929482783510.1016/j.cmet.2019.02.01130905670
     [Google Scholar]
  66. EynaudiA. Díaz-CastroF. BórquezJ.C. Bravo-SaguaR. ParraV. TroncosoR. Differential effects of oleic and palmitic acids on lipid droplet-mitochondria interaction in the hepatic cell line HepG2.Front. Nutr.2021877538210.3389/fnut.2021.77538234869541
     [Google Scholar]
  67. LeeS.J. ZhangJ. ChoiA.M.K. KimH.P. Mitochondrial dysfunction induces formation of lipid droplets as a generalized response to stress.Oxid. Med. Cell. Longev.2013201311010.1155/2013/32716724175011
     [Google Scholar]
  68. Acín-PerezR. PetcherskiA. VeliovaM. BenadorI.Y. AssaliE.A. ColleluoriG. CintiS. BrownsteinA.J. BaghdasarianS. LivhitsM.J. YehM.W. KrishnanK.C. VergnesL. WinnN.C. PadillaJ. LiesaM. SacksH.S. ShirihaiO.S. Recruitment and remodeling of peridroplet mitochondria in human adipose tissue.Redox Biol.20214610208710.1016/j.redox.2021.10208734411987
     [Google Scholar]
  69. TwigG. LiuX. LiesaM. WikstromJ.D. MolinaA.J.A. LasG. YanivG. HajnóczkyG. ShirihaiO.S. Biophysical properties of mitochondrial fusion events in pancreatic β-cells and cardiac cells unravel potential control mechanisms of its selectivity.Am. J. Physiol. Cell Physiol.20102992C477C48710.1152/ajpcell.00427.200920445168
     [Google Scholar]
  70. WillinghamT.B. AjayiP.T. GlancyB. Subcellular specialization of mitochondrial form and function in skeletal muscle cells.Front. Cell Dev. Biol.2021975730510.3389/fcell.2021.75730534722542
     [Google Scholar]
  71. KrasK.A. LanglaisP.R. HoffmanN. RoustL.R. BenjaminT.R. De FilippisE.A. DinuV. KatsanosC.S. Obesity modifies the stoichiometry of mitochondrial proteins in a way that is distinct to the subcellular localization of the mitochondria in skeletal muscle.Metabolism201889182610.1016/j.metabol.2018.09.00630253140
     [Google Scholar]
  72. KovesT.R. UssherJ.R. NolandR.C. SlentzD. MosedaleM. IlkayevaO. BainJ. StevensR. DyckJ.R.B. NewgardC.B. LopaschukG.D. MuoioD.M. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance.Cell Metab.200871455610.1016/j.cmet.2007.10.01318177724
     [Google Scholar]
  73. ZechnerR. MadeoF. KratkyD. Cytosolic lipolysis and lipophagy: two sides of the same coin.Nat. Rev. Mol. Cell Biol.2017181167168410.1038/nrm.2017.7628852221
     [Google Scholar]
  74. OgasawaraY. TsujiT. FujimotoT. Multifarious roles of lipid droplets in autophagy – Target, product, and what else?Semin. Cell Dev. Biol.2020108475410.1016/j.semcdb.2020.02.01332169402
     [Google Scholar]
  75. BarbosaA.D. SavageD.B. SiniossoglouS. Lipid droplet–organelle interactions: emerging roles in lipid metabolism.Curr. Opin. Cell Biol.201535919710.1016/j.ceb.2015.04.01725988547
     [Google Scholar]
  76. SasakiK. YoshidaH. Organelle Zones.Cell Struct. Funct.2019442859410.1247/csf.1901031308351
     [Google Scholar]
  77. Eisenberg-BordM. ShaiN. SchuldinerM. BohnertM. A tether is a tether is a tether: tethering at membrane contact sites.Dev. Cell201639439540910.1016/j.devcel.2016.10.02227875684
     [Google Scholar]
  78. TarnopolskyM.A. RennieC.D. RobertshawH.A. Fedak-TarnopolskyS.N. DevriesM.C. HamadehM.J. Influence of endurance exercise training and sex on intramyocellular lipid and mitochondrial ultrastructure, substrate use, and mitochondrial enzyme activity.Am. J. Physiol. Regul. Integr. Comp. Physiol.20072923R1271R127810.1152/ajpregu.00472.200617095651
     [Google Scholar]
  79. SturmeyR.G. O’TooleP.J. LeeseH.J. Fluorescence resonance energy transfer analysis of mitochondrial:lipid association in the porcine oocyte.Reproduction2006132682983710.1530/REP‑06‑007317127743
     [Google Scholar]
  80. ValmA.M. CohenS. LegantW.R. MelunisJ. HershbergU. WaitE. CohenA.R. DavidsonM.W. BetzigE. Lippincott-SchwartzJ. Applying systems-level spectral imaging and analysis to reveal the organelle interactome.Nature2017546765616216710.1038/nature2236928538724
     [Google Scholar]
  81. BischofJ. SalzmannM. StreubelM.K. HasekJ. GeltingerF. DuschlJ. BresgenN. BrizaP. HaskovaD. LejskovaR. SopjaniM. RichterK. RinnerthalerM. Clearing the outer mitochondrial membrane from harmful proteins via lipid droplets.Cell Death Discov.2017311701610.1038/cddiscovery.2017.1628386457
     [Google Scholar]
  82. WelteM.A. GrossS.P. PostnerM. BlockS.M. WieschausE.F. Developmental regulation of vesicle transport in Drosophila embryos: forces and kinetics.Cell199892454755710.1016/S0092‑8674(00)80947‑29491895
     [Google Scholar]
  83. XieK. ZhangP. NaH. LiuY. ZhangH. LiuP. MDT-28/PLIN-1 mediates lipid droplet-microtubule interaction via DLC-1 in Caenorhabditis elegans.Sci. Rep.2019911490210.1038/s41598‑019‑51399‑z31624276
     [Google Scholar]
  84. FujimotoY. ItabeH. SakaiJ. MakitaM. NodaJ. MoriM. HigashiY. KojimaS. TakanoT. Identification of major proteins in the lipid droplet-enriched fraction isolated from the human hepatocyte cell line HuH7.Biochim. Biophys. Acta Mol. Cell Res.200416441475910.1016/j.bbamcr.2003.10.01814741744
     [Google Scholar]
  85. LiuP. YingY. ZhaoY. MundyD.I. ZhuM. AndersonR.G.W. Chinese hamster ovary K2 cell lipid droplets appear to be metabolic organelles involved in membrane traffic.J. Biol. Chem.200427953787379210.1074/jbc.M31194520014597625
     [Google Scholar]
  86. HuangT. BamigbadeA.T. XuS. DengY. XieK. OgunsadeO.O. MirzaA.H. WangJ. LiuP. ZhangS. Identification of noncoding RNA-encoded proteins on lipid droplets.Sci. Bull. (Beijing)202166431431810.1016/j.scib.2020.09.02236654408
     [Google Scholar]
  87. ZhangS. WangY. CuiL. DengY. XuS. YuJ. CichelloS. SerreroG. YingY. LiuP. Morphologically and functionally distinct lipid droplet subpopulations.Sci. Rep.2016612953910.1038/srep2953927386790
     [Google Scholar]
  88. FujimotoY. ItabeH. KinoshitaT. HommaK.J. OnodukaJ. MoriM. YamaguchiS. MakitaM. HigashiY. YamashitaA. TakanoT. Involvement of ACSL in local synthesis of neutral lipids in cytoplasmic lipid droplets in human hepatocyte HuH7.J. Lipid Res.20074861280129210.1194/jlr.M700050‑JLR20017379924
     [Google Scholar]
  89. VargheseM. KimlerV.A. GhaziF.R. RathoreG.K. PerkinsG.A. EllismanM.H. GrannemanJ.G. Adipocyte lipolysis affects Perilipin 5 and cristae organization at the cardiac lipid droplet-mitochondrial interface.Sci. Rep.201991473410.1038/s41598‑019‑41329‑430894648
     [Google Scholar]
  90. KumarN. LeonzinoM. Hancock-CeruttiW. HorenkampF.A. LiP. LeesJ.A. WheelerH. ReinischK.M. De CamilliP. VPS13A and VPS13C are lipid transport proteins differentially localized at ER contact sites.J. Cell Biol.2018217103625363910.1083/jcb.20180701930093493
     [Google Scholar]
  91. LiuX. WeaverD. ShirihaiO. HajnóczkyG. Mitochondrial ‘kiss-and-run’: interplay between mitochondrial motility and fusion–fission dynamics.EMBO J.200928203074308910.1038/emboj.2009.25519745815
     [Google Scholar]
  92. GeltingerF. SchartelL. WiedersteinM. TeviniJ. AignerE. FelderT.K. RinnerthalerM. Friend or foe: lipid droplets as organelles for protein and lipid storage in cellular stress response, aging and disease.Molecules20202521505310.3390/molecules2521505333143278
     [Google Scholar]
  93. Thazar-PoulotN. MiquelM. Fobis-LoisyI. GaudeT. Peroxisome extensions deliver the Arabidopsis SDP1 lipase to oil bodies.Proc. Natl. Acad. Sci. USA2015112134158416310.1073/pnas.140332211225775518
     [Google Scholar]
  94. BoutantM. KulkarniS.S. JoffraudM. RatajczakJ. Valera-AlberniM. CombeR. ZorzanoA. CantóC. Mfn2 is critical for brown adipose tissue thermogenic function.EMBO J.201736111543155810.15252/embj.20169491428348166
     [Google Scholar]
  95. WangH. SreenivasanU. HuH. SaladinoA. PolsterB.M. LundL.M. GongD. StanleyW.C. SztalrydC. Perilipin 5, a lipid droplet-associated protein, provides physical and metabolic linkage to mitochondria.J. Lipid Res.201152122159216810.1194/jlr.M01793921885430
     [Google Scholar]
  96. BosmaM. MinnaardR. SparksL.M. SchaartG. LosenM. BaetsM.H. DuimelH. KerstenS. BickelP.E. SchrauwenP. HesselinkM.K.C. The lipid droplet coat protein perilipin 5 also localizes to muscle mitochondria.Histochem. Cell Biol.2012137220521610.1007/s00418‑011‑0888‑x22127648
     [Google Scholar]
  97. GrannemanJ.G. MooreH.P.H. MottilloE.P. ZhuZ. ZhouL. Interactions of perilipin-5 (Plin5) with adipose triglyceride lipase.J. Biol. Chem.201128675126513510.1074/jbc.M110.18071121148142
     [Google Scholar]
  98. StoneS.J. LevinM.C. ZhouP. HanJ. WaltherT.C. FareseR.V.Jr. The endoplasmic reticulum enzyme DGAT2 is found in mitochondria-associated membranes and has a mitochondrial targeting signal that promotes its association with mitochondria.J. Biol. Chem.200928485352536110.1074/jbc.M80576820019049983
     [Google Scholar]
  99. Bhatt-WesselB. JordanT.W. MillerJ.H. PengL. Role of DGAT enzymes in triacylglycerol metabolism.Arch. Biochem. Biophys.201865511110.1016/j.abb.2018.08.00130077544
     [Google Scholar]
  100. HuangJ. GuoD. ZhuR. FengY. LiR. YangX. ShiD. FATP1 exerts variable effects on adipogenic differentiation and proliferation in cells derived from muscle and adipose tissue.Front. Vet. Sci.2022990487910.3389/fvets.2022.90487935898540
     [Google Scholar]
  101. BeeverAT TrippTR ZhangJ MacInnisMJ NIRS-derived skeletal muscle oxidative capacity is correlated with aerobic fitness and independent of sex.J Appl. Physiol.2020129355856810.1152/japplphysiol.00017.2020
     [Google Scholar]
  102. PoppelreutherM. LundsgaardA.M. MensbergP. SjøbergK. VilsbøllT. KiensB. FüllekrugJ. Acyl- CoA synthetase expression in human skeletal muscle is reduced in obesity and insulin resistance.Physiol. Rep.20231118e1581710.14814/phy2.1581737726199
     [Google Scholar]
  103. HuangJ. ZhuR. ShiD. The role of FATP1 in lipid accumulation: a review.Mol. Cell. Biochem.202147641897190310.1007/s11010‑021‑04057‑w33486652
     [Google Scholar]
  104. QiR. LongD. WangJ. WangQ. HuangX. CaoC. GaoG. HuangJ. MicroRNA-199a targets the fatty acid transport protein 1 gene and inhibits the adipogenic trans-differentiation of C2C12 myoblasts.Cell. Physiol. Biochem.20163931087109710.1159/00044781727562723
     [Google Scholar]
  105. ChenX. LuoY. WangR. ZhouB. HuangZ. JiaG. ZhaoH. LiuG. Effects of fatty acid transport protein 1 on proliferation and differentiation of porcine intramuscular preadipocytes.Anim. Sci. J.201788573173810.1111/asj.1270127616431
     [Google Scholar]
  106. GuitartM. Osorio-ConlesÓ. PentinatT. CebriàJ. García-VilloriaJ. SalaD. SebastiánD. ZorzanoA. RibesA. Jiménez-ChillarónJ.C. García-MartínezC. Gómez-FoixA.M. Fatty acid transport protein 1 (FATP1) localizes in mitochondria in mouse skeletal muscle and regulates lipid and ketone body disposal.PLoS One201495e9810910.1371/journal.pone.009810924858472
     [Google Scholar]
  107. QiuF. XieL. MaJ. LuoW. ZhangL. ChaoZ. ChenS. NieQ. LinZ. ZhangX. Lower expression of SLC27A1 enhances intramuscular fat deposition in chicken via down-regulated fatty acid oxidation mediated by CPT1A. Front. Physiol.2017844910.3389/fphys.2017.0044928706492
     [Google Scholar]
  108. XuN. ZhangS.O. ColeR.A. McKinneyS.A. GuoF. HaasJ.T. BobbaS. FareseR.V.Jr MakH.Y. The FATP1–DGAT2 complex facilitates lipid droplet expansion at the ER–lipid droplet interface.J. Cell Biol.2012198589591110.1083/jcb.20120113922927462
     [Google Scholar]
  109. KuerschnerL. MoessingerC. ThieleC. Imaging of lipid biosynthesis: how a neutral lipid enters lipid droplets.Traffic20089333835210.1111/j.1600‑0854.2007.00689.x18088320
     [Google Scholar]
  110. ChitrajuC. WaltherT.C. FareseR.V.Jr. The triglyceride synthesis enzymes DGAT1 and DGAT2 have distinct and overlapping functions in adipocytes.J. Lipid Res.20196061112112010.1194/jlr.M09311230936184
     [Google Scholar]
  111. NingT. ZouY. YangM. LuQ. ChenM. LiuW. ZhaoS. SunY. ShiJ. MaQ. HongJ. LiuR. WangJ. NingG. Genetic interaction of DGAT2 and FAAH in the development of human obesity.Endocrine201756236637810.1007/s12020‑017‑1261‑128243972
     [Google Scholar]
  112. FriedelS. ReichwaldK. ScheragA. BrummH. WermterA.K. FriesH.R. KoberwitzK. WabitschM. MeitingerT. PlatzerM. BiebermannH. HinneyA. HebebrandJ. Mutation screen and association studies in the Diacylglycerol O-acyltransferase homolog 2 gene (DGAT2), a positional candidate gene for early onset obesity on chromosome 11q13.BMC Genet.2007811710.1186/1471‑2156‑8‑1717477860
     [Google Scholar]
  113. DejgaardS.Y. PresleyJ.F. Rab18: new insights into the function of an essential protein.Cell. Mol. Life Sci.201976101935194510.1007/s00018‑019‑03050‑330830238
     [Google Scholar]
  114. ZehmerJ.K. HuangY. PengG. PuJ. AndersonR.G.W. LiuP. A role for lipid droplets in inter-membrane lipid traffic.Proteomics20099491492110.1002/pmic.20080058419160396
     [Google Scholar]
  115. GoodmanJ.M. The gregarious lipid droplet.J. Biol. Chem.200828342280052800910.1074/jbc.R80004220018611863
     [Google Scholar]
  116. MartinS. DriessenK. NixonS.J. ZerialM. PartonR.G. Regulated localization of Rab18 to lipid droplets: effects of lipolytic stimulation and inhibition of lipid droplet catabolism.J. Biol. Chem.200528051423254233510.1074/jbc.M50665120016207721
     [Google Scholar]
  117. MartinS. PartonR.G. Lipid droplets: a unified view of a dynamic organelle.Nat. Rev. Mol. Cell Biol.20067537337810.1038/nrm191216550215
     [Google Scholar]
  118. XuD. LiY. WuL. LiY. ZhaoD. YuJ. HuangT. FergusonC. PartonR.G. YangH. LiP. Rab18 promotes lipid droplet (LD) growth by tethering the ER to LDs through SNARE and NRZ interactions.J. Cell Biol.2018217397599510.1083/jcb.20170418429367353
     [Google Scholar]
  119. TagayaM. ArasakiK. InoueH. KimuraH. Moonlighting functions of the NRZ (mammalian Dsl1) complex.Front. Cell Dev. Biol.201422510.3389/fcell.2014.0002525364732
     [Google Scholar]
  120. LaunayN. RuizM. Planas-SerraL. VerduraE. Rodríguez-PalmeroA. SchlüterA. GoicoecheaL. GuileraC. CasasJ. CampeloF. JouanguyE. CasanovaJ.L. Boespflug-TanguyO. Vazquez CancelaM. Gutiérrez-SolanaL.G. CasasnovasC. Area-GomezE. PujolA. RINT1 deficiency disrupts lipid metabolism and underlies a complex hereditary spastic paraplegia.J. Clin. Invest.202313314e16283610.1172/JCI16283637463447
     [Google Scholar]
  121. MenantA. KaressR. RZZ finds its ancestral roots.Structure201018554955010.1016/j.str.2010.04.00220462487
     [Google Scholar]
  122. DejgaardS.Y. PresleyJ.F. Interactions of lipid droplets with the intracellular transport machinery.Int. J. Mol. Sci.2021225277610.3390/ijms2205277633803444
     [Google Scholar]
  123. GaoG. ShengY. YangH. ChuaB.T. XuL. DFCP1 associates with lipid droplets.Cell Biol. Int.201943121492150410.1002/cbin.1119931293035
     [Google Scholar]
  124. PulidoM.R. Diaz-RuizA. Jiménez-GómezY. Garcia-NavarroS. Gracia- NavarroF. TinahonesF. López-MirandaJ. FrühbeckG. Vázquez-MartínezR. MalagónM.M. Rab18 dynamics in adipocytes in relation to lipogenesis, lipolysis and obesity.PLoS One201167e2293110.1371/journal.pone.002293121829560
     [Google Scholar]
  125. ShiH. SeeleyR.J. CleggD.J. Sexual differences in the control of energy homeostasis.Front. Neuroendocrinol.200930339640410.1016/j.yfrne.2009.03.00419341761
     [Google Scholar]
  126. LinY. HouX. ShenW.J. HanssenR. KhorV.K. CortezY. RosemanA.N. AzharS. KraemerF.B. SNARE-mediated cholesterol movement to mitochondria supports steroidogenesis in rodent cells.Mol. Endocrinol.201630223424710.1210/me.2015‑128126771535
     [Google Scholar]
  127. OuyangQ. ChenQ. KeS. DingL. YangX. RongP. FengW. CaoY. WangQ. LiM. SuS. WeiW. LiuM. LiuJ. ZhangX. LiJ.Z. WangH.Y. ChenS. Rab8a as a mitochondrial receptor for lipid droplets in skeletal muscle.Dev. Cell2023584289305.e610.1016/j.devcel.2023.01.00736800997
     [Google Scholar]
  128. Gallardo-MontejanoV.I. SaxenaG. KusminskiC.M. YangC. McAfeeJ.L. HahnerL. HochK. DubinskyW. NarkarV.A. BickelP.E. Nuclear Perilipin 5 integrates lipid droplet lipolysis with PGC-1α/SIRT1-dependent transcriptional regulation of mitochondrial function.Nat. Commun.2016711272310.1038/ncomms1272327554864
     [Google Scholar]
  129. HashaniM. WitzelH.R. PawellaL.M. Lehmann-KochJ. SchumacherJ. MechtersheimerG. SchnölzerM. SchirmacherP. RothW. StraubB.K. Widespread expression of perilipin 5 in normal human tissues and in diseases is restricted to distinct lipid droplet subpopulations.Cell Tissue Res.2018374112113610.1007/s00441‑018‑2845‑729752569
     [Google Scholar]
  130. NajtC.P. KhanS.A. HedenT.D. WitthuhnB.A. PerezM. HeierJ.L. MeadL.E. FranklinM.P. KaranjaK.K. GrahamM.J. MashekM.T. BernlohrD.A. ParkerL. ChowL.S. MashekD.G. Lipid droplet-derived monounsaturated fatty acids traffic via PLIN5 to allosterically activate SIRT1.Mol. Cell2020774810824.e810.1016/j.molcel.2019.12.00331901447
     [Google Scholar]
  131. ZhangE. CuiW. LoprestiM. MashekM.T. NajtC.P. HuH. MashekD.G. Hepatic PLIN5 signals via SIRT1 to promote autophagy and prevent inflammation during fasting.J. Lipid Res.202061333835010.1194/jlr.RA11900033631932301
     [Google Scholar]
  132. KienB. KolleritschS. KunowskaN. HeierC. ChalhoubG. TilpA. WolinskiH. StelzlU. HaemmerleG. Lipid droplet-mitochondria coupling via perilipin 5 augments respiratory capacity but is dispensable for FA oxidation.J. Lipid Res.202263310017210.1016/j.jlr.2022.10017235065923
     [Google Scholar]
  133. Sánchez-ÁlvarezM. del PozoM.Á. BoschM. PolA. Insights into the biogenesis and emerging functions of lipid droplets from unbiased molecular profiling approaches.Front. Cell Dev. Biol.20221090132110.3389/fcell.2022.90132135756995
     [Google Scholar]
  134. SztalrydC. BrasaemleD.L. The perilipin family of lipid droplet proteins: Gatekeepers of intracellular lipolysis.Biochim. Biophys. Acta Mol. Cell Biol. Lipids20171862101221123210.1016/j.bbalip.2017.07.00928754637
     [Google Scholar]
  135. PribasnigM. KienB. PuschL. HaemmerleG. ZimmermannR. WolinskiH. Extended-resolution imaging of the interaction of lipid droplets and mitochondria.Biochim. Biophys. Acta Mol. Cell Biol. Lipids20181863101285129610.1016/j.bbalip.2018.07.00830305245
     [Google Scholar]
  136. WangH. SztalrydC. Oxidative tissue: perilipin 5 links storage with the furnace.Trends Endocrinol. Metab.201122619720310.1016/j.tem.2011.03.00821632259
     [Google Scholar]
  137. SandersM.A. MadouxF. MladenovicL. ZhangH. YeX. AngrishM. MottilloE.P. CarusoJ.A. HalvorsenG. RoushW.R. ChaseP. HodderP. GrannemanJ.G. Endogenous and synthetic ABHD5 ligands regulate ABHD5-perilipin interactions and lipolysis in fat and muscle.Cell Metab.201522585186010.1016/j.cmet.2015.08.02326411340
     [Google Scholar]
  138. TanY. JinY. WangQ. HuangJ. WuX. RenZ. Perilipin 5 protects against cellular oxidative stress by enhancing mitochondrial function in HepG2 cells.Cells2019810124110.3390/cells810124131614673
     [Google Scholar]
  139. ZhuY. ZhangX. ZhangL. ZhangM. LiL. LuoD. ZhongY. Perilipin5 protects against lipotoxicity and alleviates endoplasmic reticulum stress in pancreatic β- cells.Nutr. Metab. (Lond.)20191615010.1186/s12986‑019‑0375‑231384284
     [Google Scholar]
  140. KimmelA.R. SztalrydC. Perilipin 5, a lipid droplet protein adapted to mitochondrial energy utilization.Curr. Opin. Lipidol.201425211011710.1097/MOL.000000000000005724535284
     [Google Scholar]
  141. LinJ. ChenA. Perilipin 5 restores the formation of lipid droplets in activated hepatic stellate cells and inhibits their activation.Lab. Invest.201696779180610.1038/labinvest.2016.5327135793
     [Google Scholar]
  142. Bombarda-RochaV. SilvaD. Badr-EddineA. NogueiraP. GonçalvesJ. FrescoP. Challenges in pharmacological intervention in perilipins (PLINs) to modulate lipid droplet dynamics in obesity and cancer.Cancers20231515401310.3390/cancers1515401337568828
     [Google Scholar]
  143. MasonR.R. MokhtarR. MatzarisM. SelathuraiA. KowalskiG.M. MokbelN. MeikleP.J. BruceC.R. WattM.J. PLIN5 deletion remodels intracellular lipid composition and causes insulin resistance in muscle.Mol. Metab.20143665266310.1016/j.molmet.2014.06.00225161888
     [Google Scholar]
  144. WolinsN.E. QuaynorB.K. SkinnerJ.R. TzekovA. CroceM.A. GroplerM.C. VarmaV. Yao-BorengasserA. RasouliN. KernP.A. FinckB.N. BickelP.E. OXPAT/PAT-1 is a PPAR-induced lipid droplet protein that promotes fatty acid utilization.Diabetes200655123418342810.2337/db06‑039917130488
     [Google Scholar]
  145. Gallardo-MontejanoV.I. YangC. HahnerL. McAfeeJ.L. JohnsonJ.A. HollandW.L. Fernandez-ValdiviaR. BickelP.E. Perilipin 5 links mitochondrial uncoupled respiration in brown fat to healthy white fat remodeling and systemic glucose tolerance.Nat. Commun.2021121332010.1038/s41467‑021‑23601‑234083525
     [Google Scholar]
  146. LaurensC. BourlierV. MairalA. LoucheK. BadinP.M. MouiselE. MontagnerA. MaretteA. TremblayA. WeisnagelJ.S. GuillouH. LanginD. JoanisseD.R. MoroC. Perilipin 5 fine-tunes lipid oxidation to metabolic demand and protects against lipotoxicity in skeletal muscle.Sci. Rep.2016613831010.1038/srep3831027922115
     [Google Scholar]
  147. MortonT.L. GaliorK. McGrathC. WuX. UzerG. UzerG.B. SenB. XieZ. TysonD. RubinJ. StynerM. Exercise Increases and Browns Muscle Lipid in High- Fat Diet-Fed Mice.Front. Endocrinol. (Lausanne)201678010.3389/fendo.2016.0008027445983
     [Google Scholar]
  148. GemminkA. DaemenS. BrouwersB. HuntjensP.R. SchaartG. Moonen-KornipsE. JörgensenJ. HoeksJ. SchrauwenP. HesselinkM.K.C. Dissociation of intramyocellular lipid storage and insulin resistance in trained athletes and type 2 diabetes patients; involvement of perilipin 5?J. Physiol.2018596585786810.1113/JP27518229110300
     [Google Scholar]
  149. MaY. YinX. QinZ. KeX. MiY. ZhengP. TangY. Role of Plin5 deficiency in progression of non-alcoholic fatty liver disease induced by a high-fat diet in mice.J. Comp. Pathol.2021189889710.1016/j.jcpa.2021.10.00234886991
     [Google Scholar]
  150. AsimakopoulouA. EngelK.M. GasslerN. BrachtT. SitekB. BuhlE.M. KalampokaS. Pinoé-SchmidtM. van HeldenJ. SchillerJ. WeiskirchenR. Deletion of perilipin 5 protects against hepatic injury in nonalcoholic fatty liver disease via missing inflammasome activation.Cells202096134610.3390/cells906134632481590
     [Google Scholar]
  151. FachadaV. RahkilaP. FachadaN. TurpeinenT. KujalaU.M. KainulainenH. Enlarged PLIN5-uncoated lipid droplets in inner regions of skeletal muscle type II fibers associate with type 2 diabetes.Acta Histochem.2022124315186910.1016/j.acthis.2022.15186935220055
     [Google Scholar]
  152. JägerströmS. PolesieS. WickströmY. JohanssonB.R. SchröderH.D. HøjlundK. BoströmP. Lipid droplets interact with mitochondria using SNAP23.Cell Biol. Int.200933993494010.1016/j.cellbi.2009.06.01119524684
     [Google Scholar]
  153. StraussJ.A. ShawC.S. BradleyH. WilsonO.J. DorvalT. PillingJ. WagenmakersA.J.M. Immunofluorescence microscopy of SNAP23 in human skeletal muscle reveals colocalization with plasma membrane, lipid droplets, and mitochondria.Physiol. Rep.201641e1266210.14814/phy2.1266226733245
     [Google Scholar]
  154. BoströmP. AnderssonL. RutbergM. PermanJ. LidbergU. JohanssonB.R. Fernandez-RodriguezJ. EricsonJ. NilssonT. BorénJ. OlofssonS.O. SNARE proteins mediate fusion between cytosolic lipid droplets and are implicated in insulin sensitivity.Nat. Cell Biol.20079111286129310.1038/ncb164817922004
     [Google Scholar]
  155. MillershipS. NinkinaN. GuschinaI.A. NortonJ. BrambillaR. OortP.J. AdamsS.H. DennisR.J. VosholP.J. RochfordJ.J. BuchmanV.L. Increased lipolysis and altered lipid homeostasis protect γ-synuclein–null mutant mice from diet-induced obesity.Proc. Natl. Acad. Sci. USA201210951209432094810.1073/pnas.121002211023213245
     [Google Scholar]
  156. MillershipS. NinkinaN. RochfordJ.J. BuchmanV.L. γ-synuclein is a novel player in the control of body lipid metabolism.Adipocyte20132427628010.4161/adip.2516224052906
     [Google Scholar]
  157. YoungP.A. SenkalC.E. SuchanekA.L. GrevengoedT.J. LinD.D. ZhaoL. CrunkA.E. KlettE.L. FüllekrugJ. ObeidL.M. ColemanR.A. Long-chain acyl-CoA synthetase 1 interacts with key proteins that activate and direct fatty acids into niche hepatic pathways.J. Biol. Chem.201829343167241674010.1074/jbc.RA118.00404930190326
     [Google Scholar]
  158. SohnJ.H. LeeY.K. HanJ.S. JeonY.G. KimJ.I. ChoeS.S. KimS.J. YooH.J. KimJ.B. Perilipin 1 (Plin1) deficiency promotes inflammatory responses in lean adipose tissue through lipid dysregulation.J. Biol. Chem.201829336139741398810.1074/jbc.RA118.00354130042231
     [Google Scholar]
  159. MuñozJ.P. BaseiF.L. RojasM.L. GalvisD. ZorzanoA. Mechanisms of Modulation of Mitochondrial Architecture.Biomolecules2023138122510.3390/biom1308122537627290
     [Google Scholar]
  160. JuL. HanJ. ZhangX. DengY. YanH. WangC. LiX. ChenS. AlimujiangM. LiX. FangQ. YangY. JiaW. Obesity-associated inflammation triggers an autophagy–lysosomal response in adipocytes and causes degradation of perilipin 1.Cell Death Dis.201910212110.1038/s41419‑019‑1393‑830741926
     [Google Scholar]
  161. WeiS. LiuS. SuX. WangW. LiF. DengJ. LyuY. GengB. XuG. Spontaneous development of hepatosteatosis in perilipin-1 null mice with adipose tissue dysfunction.Biochim. Biophys. Acta Mol. Cell Biol. Lipids20181863221221810.1016/j.bbalip.2017.11.00729191637
     [Google Scholar]
  162. LiuS. GengB. ZouL. WeiS. WangW. DengJ. XuC. ZhaoX. LyuY. SuX. XuG. Development of hypertrophic cardiomyopathy in perilipin-1 null mice with adipose tissue dysfunction.Cardiovasc. Res.20151051203010.1093/cvr/cvu21425416668
     [Google Scholar]
  163. LangloisD. ForcheronF. LiJ.Y. del CarmineP. NeggaziS. BeylotM. Increased atherosclerosis in mice deficient in perilipin1.Lipids Health Dis.201110116910.1186/1476‑511X‑10‑16921943217
     [Google Scholar]
  164. de BritoO.M. ScorranoL. Mitofusin 2 tethers endoplasmic reticulum to mitochondria.Nature2008456722260561010.1038/nature0753419052620
     [Google Scholar]
  165. GiacomelloM. PyakurelA. GlytsouC. ScorranoL. The cell biology of mitochondrial membrane dynamics.Nat. Rev. Mol. Cell Biol.202021420422410.1038/s41580‑020‑0210‑732071438
     [Google Scholar]
  166. Hernández-AlvarezM.I. SebastiánD. VivesS. IvanovaS. BartoccioniP. KakimotoP. PlanaN. VeigaS.R. HernándezV. VasconcelosN. PeddintiG. AdroverA. JovéM. PamplonaR. Gordaliza-AlagueroI. CalvoE. CabréN. CastroR. KuzmanicA. BoutantM. SalaD. HyotylainenT. OrešičM. FortJ. Errasti-MurugarrenE. RodríguesC.M.P. OrozcoM. JovenJ. CantóC. PalacinM. Fernández-VeledoS. VendrellJ. ZorzanoA. Deficient endoplasmic reticulum-mitochondrial phosphatidylserine transfer causes liver disease.Cell20191774881895.e1710.1016/j.cell.2019.04.01031051106
     [Google Scholar]
  167. ManciniG. PirruccioK. YangX. BlüherM. RodehefferM. HorvathT.L. Mitofusin 2 in mature adipocytes controls adiposity and body weight.Cell Rep.2019261128492858.e410.1016/j.celrep.2019.02.03930865877
     [Google Scholar]
  168. SidaralaV. ZhuJ. Levi-D’AnconaE. PearsonG.L. ReckE.C. WalkerE.M. KaufmanB.A. SoleimanpourS.A. Mitofusin 1 and 2 regulation of mitochondrial DNA content is a critical determinant of glucose homeostasis.Nat. Commun.2022131234010.1038/s41467‑022‑29945‑735487893
     [Google Scholar]
  169. BachD. NaonD. PichS. SorianoF.X. VegaN. RieussetJ. LavilleM. GuilletC. BoirieY. Wallberg-HenrikssonH. MancoM. CalvaniM. CastagnetoM. PalacínM. MingroneG. ZierathJ.R. VidalH. ZorzanoA. Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle: effects of type 2 diabetes, obesity, weight loss, and the regulatory role of tumor necrosis factor alpha and interleukin-6.Diabetes20055492685269310.2337/diabetes.54.9.268516123358
     [Google Scholar]
  170. SebastiánD. Hernández-AlvarezM.I. SegalésJ. SorianelloE. MuñozJ.P. SalaD. WagetA. LiesaM. PazJ.C. GopalacharyuluP. OrešičM. PichS. BurcelinR. PalacínM. ZorzanoA. Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis.Proc. Natl. Acad. Sci. USA2012109145523552810.1073/pnas.110822010922427360
     [Google Scholar]
  171. SebastiánD. ZorzanoA. When MFN2 (mitofusin 2) met autophagy: A new age for old muscles.Autophagy201612112250225110.1080/15548627.2016.121538327575337
     [Google Scholar]
  172. ChenY. DornG.W.II PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria.Science2013340613147147510.1126/science.123103123620051
     [Google Scholar]
  173. RaudenskaM. GumulecJ. BalvanJ. MasarikM. Caveolin-1 in oncogenic metabolic symbiosis.Int. J. Cancer202014771793180710.1002/ijc.3298732196654
     [Google Scholar]
  174. NwosuZ.C. EbertM.P. DooleyS. MeyerC. Caveolin-1 in the regulation of cell metabolism: a cancer perspective.Mol. Cancer20161517110.1186/s12943‑016‑0558‑727852311
     [Google Scholar]
  175. Núñez-WehingerS. OrtizR.J. DíazN. DíazJ. Lobos- GonzálezL. QuestA.F.G. Caveolin-1 in cell migration and metastasis.Curr. Mol. Med.201414225527410.2174/156652401466614012811282724467203
     [Google Scholar]
  176. WangS. IchinomiyaT. TeradaY. WangD. PatelH.H. HeadB.P. Synapsin-promoted caveolin-1 overexpression maintains mitochondrial morphology and function in PSAPP alzheimer’s disease mice.Cells2021109248710.3390/cells1009248734572135
     [Google Scholar]
  177. YuD.M. JungS.H. AnH.T. LeeS. HongJ. ParkJ.S. LeeH. LeeH. BahnM.S. LeeH.C. HanN.K. KoJ. LeeJ.S. KoY.G. Caveolin-1 deficiency induces premature senescence with mitochondrial dysfunction.Aging Cell201716477378410.1111/acel.1260628514055
     [Google Scholar]
  178. IlhaM. Meira MartinsL.A. da Silveira MoraesK. DiasC.K. ThoméM.P. PetryF. RohdenF. BorojevicR. TrindadeV.M.T. KlamtF. Barbé-TuanaF. LenzG. GumaF.C.R. Caveolin-1 influences mitochondrial plasticity and function in hepatic stellate cell activation.Cell Biol. Int.202246111787180010.1002/cbin.1187635971753
     [Google Scholar]
  179. CohenA.W. RazaniB. SchubertW. WilliamsT.M. WangX.B. IyengarP. BrasaemleD.L. SchererP.E. LisantiM.P. Role of caveolin-1 in the modulation of lipolysis and lipid droplet formation.Diabetes20045351261127010.2337/diabetes.53.5.126115111495
     [Google Scholar]
  180. LiuI.F. LinT.C. WangS.C. YenC.H. LiC.Y. KuoH.F. HsiehC.C. ChangC.Y. ChangC.R. ChenY.H. LiuY.R. LeeT.Y. HuangC.Y. HsuC.H. LinS.J. LiuP.L. Long-term administration of Western diet induced metabolic syndrome in mice and causes cardiac microvascular dysfunction, cardiomyocyte mitochondrial damage, and cardiac remodeling involving caveolae and caveolin-1 expression.Biol. Direct2023181910.1186/s13062‑023‑00363‑z36879344
     [Google Scholar]
  181. AbajF. MirzaeiK. Caveolin-1 genetic polymorphism interacts with PUFA to modulate metabolic syndrome risk.Br. J. Nutr.202212791281128810.1017/S000711452100222134155967
     [Google Scholar]
  182. AbajF. MirzababaeiA. HosseininasabD. BahrampourN. ClarkC.C.T. MirzaeiK. Interactions between Caveolin-1 polymorphism and Plant-based dietary index on metabolic and inflammatory markers among women with obesity.Sci. Rep.2022121908810.1038/s41598‑022‑12913‑y35641515
     [Google Scholar]
  183. AaliY. ShirasebF. AbajF. koohdaniF. MirzaeiK. The interactions between dietary fats intake and Caveolin 1 rs 3807992 polymorphism with fat distribution in overweight and obese women: a cross-sectional study.BMC Med. Genomics202114126510.1186/s12920‑021‑01114‑734753501
     [Google Scholar]
  184. AbajF. KoohdaniF. RafieeM. AlvandiE. YekaninejadM.S. MirzaeiK. Interactions between Caveolin-1 (rs3807992) polymorphism and major dietary patterns on cardio-metabolic risk factors among obese and overweight women.BMC Endocr. Disord.202121113810.1186/s12902‑021‑00800‑y34210318
     [Google Scholar]
  185. BaudrandR. GoodarziM.O. VaidyaA. UnderwoodP.C. WilliamsJ.S. JeunemaitreX. HopkinsP.N. BrownN. RabyB.A. Lasky-SuJ. AdlerG.K. CuiJ. GuoX. TaylorK.D. ChenY.D.I. XiangA. RaffelL.J. BuchananT.A. RotterJ.I. WilliamsG.H. PojogaL.H. A prevalent caveolin-1 gene variant is associated with the metabolic syndrome in Caucasians and Hispanics.Metabolism201564121674168110.1016/j.metabol.2015.09.00526475177
     [Google Scholar]
  186. ChenS. WangX. WangJ. ZhaoY. WangD. TanC. FaJ. ZhangR. WangF. XuC. HuangY. LiS. YinD. XiongX. LiX. ChenQ. TuX. YangY. XiaY. XuC. WangQ.K. Genomic variant in CAV1 increases susceptibility to coronary artery disease and myocardial infarction.Atherosclerosis201624614815610.1016/j.atherosclerosis.2016.01.00826775120
     [Google Scholar]
  187. EngelmanJ.A. ChuC. LinA. JoH. IkezuT. OkamotoT. KohtzD.S. LisantiM.P. Caveolin-mediated regulation of signaling along the p42/44 MAP kinase cascade in vivo.FEBS Lett.1998428320521110.1016/S0014‑5793(98)00470‑09654135
     [Google Scholar]
  188. Mora-GarcíaG. Gómez-CamargoD. AlarioÁ. Gómez-AlegríaC. A Common variation in the caveolin 1 gene is associated with high serum triglycerides and metabolic syndrome in an admixed latin american population.Metab. Syndr. Relat. Disord.201816945346310.1089/met.2018.000429762069
     [Google Scholar]
  189. HongZ. AdlakhaJ. WanN. GuinnE. GiskaF. GuptaK. MeliaT.J. ReinischK.M. Mitoguardin-2–mediated lipid transfer preserves mitochondrial morphology and lipid droplet formation.J. Cell Biol.202222112e20220702210.1083/jcb.20220702236282247
     [Google Scholar]
  190. ZhangY. LiuX. BaiJ. TianX. ZhaoX. LiuW. DuanX. ShangW. FanH.Y. TongC. Mitoguardin regulates mitochondrial fusion through mitopld and is required for neuronal homeostasis.Mol. Cell201661111112410.1016/j.molcel.2015.11.01726711011
     [Google Scholar]
  191. AndingA.L. WangC. ChangT.K. SliterD.A. PowersC.M. HofmannK. YouleR.J. BaehreckeE.H. Vps13D encodes a ubiquitin-binding protein that is required for the regulation of mitochondrial size and clearance.Curr. Biol.2018282287295.e610.1016/j.cub.2017.11.06429307555
     [Google Scholar]
  192. SeongE. InsoleraR. DulovicM. KamsteegE.J. TrinhJ. BrüggemannN. SandfordE. LiS. OzelA.B. LiJ.Z. JewettT. KievitA.J.A. MünchauA. ShakkottaiV. KleinC. CollinsC.A. LohmannK. van de WarrenburgB.P. BurmeisterM. Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects.Ann. Neurol.20188361075108810.1002/ana.2522029604224
     [Google Scholar]
  193. LiP. LeesJ.A. LuskC.P. ReinischK.M. Cryo-EM reconstruction of a VPS13 fragment reveals a long groove to channel lipids between membranes.J. Cell Biol.20202195e20200116110.1083/jcb.20200116132182622
     [Google Scholar]
  194. MaedaS. OtomoC. OtomoT. The autophagic membrane tether ATG2A transfers lipids between membranes.eLife20198e4577710.7554/eLife.4577731271352
     [Google Scholar]
  195. ValverdeD.P. YuS. BoggavarapuV. KumarN. LeesJ.A. WalzT. ReinischK.M. MeliaT.J. ATG2 transports lipids to promote autophagosome biogenesis.J. Cell Biol.201921861787179810.1083/jcb.20181113930952800
     [Google Scholar]
  196. OsawaT. KotaniT. KawaokaT. HirataE. SuzukiK. NakatogawaH. OhsumiY. NodaN.N. Atg2 mediates direct lipid transfer between membranes for autophagosome formation.Nat. Struct. Mol. Biol.201926428128810.1038/s41594‑019‑0203‑430911189
     [Google Scholar]
  197. LeesJ.A. ReinischK.M. Inter-organelle lipid transfer: a channel model for Vps13 and chorein-N motif proteins.Curr. Opin. Cell Biol.202065667110.1016/j.ceb.2020.02.00832213462
     [Google Scholar]
  198. UgurB. Hancock-CeruttiW. LeonzinoM. De CamilliP. Role of VPS13, a protein with similarity to ATG2, in physiology and disease.Curr. Opin. Genet. Dev.202065616810.1016/j.gde.2020.05.02732563856
     [Google Scholar]
  199. Guillén-SamanderA. LeonzinoM. HannaM.G.IV TangN. ShenH. De CamilliP. VPS13D bridges the ER to mitochondria and peroxisomes via Miro.J. Cell Biol.20212205e20201000410.1083/jcb.20201000433891013
     [Google Scholar]
  200. HungV. LamS.S. UdeshiN.D. SvinkinaT. GuzmanG. MoothaV.K. CarrS.A. TingA.Y. Proteomic mapping of cytosol-facing outer mitochondrial and ER membranes in living human cells by proximity biotinylation.eLife20176e2446310.7554/eLife.2446328441135
     [Google Scholar]
  201. LiuX. SalokasK. TameneF. JiuY. WeldatsadikR.G. ÖhmanT. VarjosaloM. An AP-MS- and BioID- compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations.Nat. Commun.201891118810.1038/s41467‑018‑03523‑229568061
     [Google Scholar]
  202. AntonickaH. LinZ.Y. JanerA. AaltonenM.J. WeraarpachaiW. GingrasA.C. ShoubridgeE.A. A high- density human mitochondrial proximity interaction network.Cell Metab.2020323479497.e910.1016/j.cmet.2020.07.01732877691
     [Google Scholar]
  203. WangJ. FangN. XiongJ. DuY. CaoY. JiW.K. An ESCRT-dependent step in fatty acid transfer from lipid droplets to mitochondria through VPS13D−TSG101 interactions.Nat. Commun.2021121125210.1038/s41467‑021‑21525‑533623047
     [Google Scholar]
  204. OlkkonenV.M. LiS. Oxysterol-binding proteins: Sterol and phosphoinositide sensors coordinating transport, signaling and metabolism.Prog. Lipid Res.201352452953810.1016/j.plipres.2013.06.00423830809
     [Google Scholar]
  205. JoshiA.S. ThompsonM.N. FeiN. HüttemannM. GreenbergM.L. Cardiolipin and mitochondrial phosphatidylethanolamine have overlapping functions in mitochondrial fusion in Saccharomyces cerevisiae.J. Biol. Chem.201228721175891759710.1074/jbc.M111.33016722433850
     [Google Scholar]
  206. GalmesR. HoucineA. van VlietA.R. AgostinisP. JacksonC.L. GiordanoF. ORP5/ORP8 localize to endoplasmic reticulum–mitochondria contacts and are involved in mitochondrial function.EMBO Rep.201617680081010.15252/embr.20154110827113756
     [Google Scholar]
  207. Monteiro-CardosoV.F. RochinL. AroraA. HoucineA. JääskeläinenE. KiveläA.M. SauvanetC. Le BarsR. MarienE. DehairsJ. NeveuJ. El KhalloukiN. SantonicoE. SwinnenJ.V. TaresteD. OlkkonenV.M. GiordanoF. ORP5/8 and MIB/MICOS link ER-mitochondria and intra-mitochondrial contacts for non-vesicular transport of phosphatidylserine.Cell Rep.2022401211136410.1016/j.celrep.2022.11136436130504
     [Google Scholar]
  208. DuX. ZhouL. AwY.C. MakH.Y. XuY. RaeJ. WangW. ZadoorianA. HancockS.E. OsborneB. ChenX. WuJ.W. TurnerN. PartonR.G. LiP. YangH. ORP5 localizes to ER–lipid droplet contacts and regulates the level of PI(4)P on lipid droplets.J. Cell Biol.20202191e20190516210.1083/jcb.20190516231653673
     [Google Scholar]
  209. SaloV.T. IkonenE. Moving out but keeping in touch: Contacts between endoplasmic reticulum and lipid droplets.Curr. Opin. Cell Biol.201957647010.1016/j.ceb.2018.11.00230476754
     [Google Scholar]
  210. SaloV.T. LiS. VihinenH. Hölttä-VuoriM. SzkalisityA. HorvathP. BelevichI. PeränenJ. ThieleC. SomerharjuP. ZhaoH. SantinhoA. ThiamA.R. JokitaloE. IkonenE. Seipin facilitates triglyceride flow to lipid droplet and counteracts droplet ripening via endoplasmic reticulum contact.Dev. Cell2019504478493.e910.1016/j.devcel.2019.05.01631178403
     [Google Scholar]
  211. WangH. BecuweM. HousdenB.E. ChitrajuC. PorrasA.J. GrahamM.M. LiuX.N. ThiamA.R. SavageD.B. AgarwalA.K. GargA. OlarteM.J. LinQ. FröhlichF. Hannibal-BachH.K. UpadhyayulaS. PerrimonN. KirchhausenT. EjsingC.S. WaltherT.C. FareseR.V.Jr Seipin is required for converting nascent to mature lipid droplets.eLife20165e1658210.7554/eLife.1658227564575
     [Google Scholar]
  212. MardaniI. Tomas DalenK. DrevingeC. MiljanovicA. StåhlmanM. KlevstigM. Scharin TängM. FogelstrandP. LevinM. EkstrandM. NairS. RedforsB. OmerovicE. AnderssonL. KimmelA.R. BorénJ. LevinM.C. Plin2-deficiency reduces lipophagy and results in increased lipid accumulation in the heart.Sci. Rep.201991690910.1038/s41598‑019‑43335‑y31061399
     [Google Scholar]
  213. ZhangY. LinS. PengJ. LiangX. YangQ. BaiX. LiY. LiJ. DongW. WangY. HuangY. PeiY. GuoJ. ZhaoW. ZhangZ. LiuM. ZhuA.J. Amelioration of hepatic steatosis by dietary essential amino acid-induced ubiquitination.Mol. Cell20228281528- 1542.e1010.1016/j.molcel.2022.01.02135245436
     [Google Scholar]
  214. VasevaA.V. MollU.M. Identification of p53 in mitochondria.Methods Mol. Biol.2013962758410.1007/978‑1‑62703‑236‑0_623150438
     [Google Scholar]
  215. CheL. HuangJ. LinJ.X. XuC.Y. WuX.M. DuZ.B. WuJ.S. LinZ.N. LinY.C. Aflatoxin B1 exposure triggers hepatic lipotoxicity via p53 and perilipin 2 interaction-mediated mitochondria-lipid droplet contacts: An in vitro and in vivo assessment.J. Hazard. Mater.202344513058410.1016/j.jhazmat.2022.13058437055989
     [Google Scholar]
  216. BrownsteinA.J. VeliovaM. Acin-PerezR. VillalobosF. PetcherskiA. TombolatoA. LiesaM. ShirihaiO.S. Mitochondria isolated from lipid droplets of white adipose tissue reveal functional differences based on lipid droplet size.Life Sci. Alliance202472e20230193410.26508/lsa.20230193438056907
     [Google Scholar]
/content/journals/cmc/10.2174/0109298673309247240610050423
Loading
Mitochondria and Lipid Droplets: Focus on the Molecular Structure of Contact Sites in the Pathogenesis of Metabolic Syndrome
Curr. Med. Chem. 32, 3006 (2025); https://doi.org/10.2174/0109298673309247240610050423
/content/journals/cmc/10.2174/0109298673309247240610050423
/content/journals/cmc/10.2174/0109298673309247240610050423
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): fatty; insulin resistance; lipid droplet; liver disease; Metabolic syndrome; mitochondria

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test