More than a powerplant: the influence of mitochondrial transfer on the epigenome

Each cell in the human body, with the exception of red blood cells, contains multiple copies of mitochondria that house their own genetic material, the maternally inherited mitochondrial DNA. Mitochondria are the cell's powerplant due to their massive ATP generation. However, the mitochondrion is also a hub for metabolite production from the TCA cycle, fatty acid beta-oxidation, and ketogenesis. In addition to producing macromolecules for biosynthetic reactions and cell replication, several mitochondrial intermediate metabolites serve as cofactors or substrates for epigenome modifying enzymes that regulate chromatin structure and impact gene expression. Here, we discuss connections between mitochondrial metabolites and enzymatic writers and erasers of chromatin modifications. We do this from the unique perspective of cell-to-cell mitochondrial transfer and its potential impact on mitochondrial replacement therapies.