Mitochondria and the epigenome: maternal co-inheritance and crosstalk from oocyte to embryo

Mitochondria, as central hubs of metabolism and bioenergetics, are essential for oocyte maturation and early embryonic development. Their functions are intricately linked to epigenetic mechanisms, forming interconnected networks that govern gene expression across both nuclear and mitochondrial genomes. Mitochondrial epigenetic programming established during oogenesis is transmitted maternally through cytoplasmic inheritance, underscoring mitochondrial quality as a heritable determinant of developmental competence. Expanding research has broadened epigenetic regulation beyond the nucleus, showing that mitochondrial DNA (mtDNA) also undergoes dynamic modifications, including methylation, which offer fresh insights into bidirectional mitochondrial-nuclear communication. This review highlights how nuclear and mitochondrial genomes mutually influence one another in terms of mitochondrial function and epigenetic landscape. We particularly discuss advance in mtDNA methylation, its inheritance during oogenesis, and the contribution of accumulating mitochondrial mutations. Finally, we outline how diverse epigenetic regulators shape mitochondrial physiology and how mitochondrial metabolism and composition, in turn, feedback on the epigenome during development.