Abstract

Hundreds to thousands of mitochondrial genome copies are normally present in each cell. However, a fraction of these genomes can acquire pathogenic mutations and coexist with wildtype copies. We sought to determine the cellular forces that allow mutant genomes to persist. Given the central role of mitochondria in metabolism, we reasoned that mitochondrial genome dynamics might be sensitive to nutritional conditions. Using model system C. elegans, we find that mutant genomes lose their competitive advantage over wildtype genomes within the female germline under conditions of caloric restriction. Our subsequent genetic and cellular analyses show that this is because mutant genomes sense and exploit nutrition sensing pathways. We are currently exploring the molecular mechanisms that underlie the ability of mutant genomes to exploit nutrition. Taken together, our work suggests that environmental context of diet and nutrition can play an important role in modulating the mitochondrial genotype.