Figure 3.

Model of genomic balance. At any given stage in development, for a cell to be ultimately functional, it needs to establish genomic balance. There is a continual flow of regulatory information between the nucleus and the mitochondrial genome that ensures there are sufficient copies of mtDNA to meet a cell’s functional requirements for ATP through OXPHOS. At the level of the nuclear genome, genomic balance is mediated by epigenetic changes, for example the levels of DNA methylation, which control gene expression. Other factors include DNA rearrangements, such as mutations and deletions, and copy number variants. At the level of the mitochondrial genome, the choice of cellular metabolism will affect mtDNA copy number, which, in turn, is aided by the cell’s mtDNA genotype. As a result, metabolic factors are released which can modulate DNA methylation and other epigenetic modifiers that regulate both the nuclear and mitochondrial genomes.