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Human mitochondrial DNA (mtDNA) stands at the nexus of scientific intrigue and controversy, owing to its distinctive genetic features and indispensable role in cellular energy dynamics. This narrative review explores the complexities, controversies, and key issues in current research on human mtDNA. A comprehensive search on literature spanning from January 2000 to January 2025 was conducted across electronic databases including PubMed, Scopus, Web of Science, and Google Scholar. Keywords such as “mitochondrial DNA,” “mtDNA mutations,” “mtDNA inheritance,” “mitochondrial genetics,” “mitochondrial diseases,” and “future perspectives of mtDNA” were used to identify relevant studies published in peer-reviewed journals, books, and reputable conference proceedings. Articles selected for inclusion were limited to those written in English and focused on human mtDNA research. Review articles, original research papers, meta-analyses, and authoritative texts were prioritized. Information extracted from selected studies was synthesized to provide a comprehensive overview. The synthesized data were critically analyzed to highlight emerging trends, unresolved controversies, and future research directions in the field of mtDNA research. Decoding the complexities of human mtDNA offers profound insights into fundamental biological processes and evolutionary history. This review emphasizes the ongoing significance of mtDNA research in shaping the future of biomedical sciences and highlights the importance of continued exploration into its intricate molecular code.
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