Tissue-Specific Heteroplasmy Segregation is Accompanied by a Sharp Mitochondrial Genome Decline in Caenorhabditis Elegans Soma
Tsyba, Nikita
0009-0001-5716-8395
:
2023-05-09
Abstract
Mutations in the mitochondrial genome (mtDNA) can be pathogenic. Due to the multicopy nature of mtDNA, wild-type copies can compensate for the effects of mutant mtDNA. The number of wildtype copies available for compensation varies depending on the mutant load and the total copy number. Here, we examine both mutant load and copy number in the tissues of Caenorhabditis elegans. We found that neurons, but not muscles, have modestly higher mutant load than rest of the soma. We also uncovered the different effect of aak-2 knockout on the mutant load in the two tissues. The most surprising result, however, was a sharp mtDNA decline in the C. elegans soma. We discovered that somatic mtDNA numbers drop sharply during development and continue to decline with age. Nevertheless, the worms complete their life cycle despite the mtDNA losses. We used a simple mathematical model to explore the factors that may help worms tolerate the sharp drop in mtDNA content. Our results suggest that low sensitivity to ETC protein losses, in combination with high ETC protein stability may reduce the need to maintain mtDNA for short-living organisms, like C. elegans.