Genomic balance: two genomes establishing synchrony to modulate cellular fate and function

Abstract

It is becoming increasingly apparent that cells require cooperation between the nuclear and mitochondrial genomes to promote effective function. However, it was long thought that the mitochondrial genome was under the strict control of the nuclear genome and the mitochondrial genome had little influence on cell fate unless it was extensively mutated, as in the case of the mitochondrial DNA diseases. However, as our understanding of the roles that epigenetic regulators, including DNA methylation, and metabolism play in cell fate and function, the role of the mitochondrial genome appears to have a greater influence than previously thought. In this review, I draw on examples from tumorigenesis, stem cells, and oocyte pre- and post-fertilisation events to discuss how modulating one genome affects the other and that this results in a compromise to produce functional mature cells. I propose that, during development, both of the genomes interact with each other through intermediaries to establish genomic balance and that establishing genomic balance is a key facet in determining cell fate and viability.