Experimental Evolution Improves Mitochondrial Genome Quality Control in Saccharomyces Cerevisiae and Extends Its Replicative Lifespan
28 Pages Posted: 24 Mar 2021 Publication Status: Published
More...Abstract
The mitochondrion is an ancient endosymbiotic organelle that performs many essential functions in eukaryotic cells. Mitochondrial impairment often results in physiological defects or diseases. Since most mitochondrial genes have been copied into the nuclear genome during evolution, the regulatory and interactionary mechanisms between the mitochondrial and nuclear genomes are very complex. Various mechanisms have been shown to monitor the quality and quantity of mitochondria. Nonetheless, it remains unclear if these pathways can be further modified to enhance mitochondrial stability. We experimentally evolved yeast cells under conditions that selected for efficient respiration while continuously assaulting the mitochondrial genome (mtDNA) with ethidium bromide (EtBr). We found that mtDNA stability was enhanced in most of the evolved lines despite being challenged with damage reagents. We identified mutations of the mitochondrial NADH dehydrogenase NDE1 in most of the evolved lines, but other pathways are also involved. Finally, we show that cells displaying enhanced mtDNA stability also exhibit a prolonged replicative lifespan. Our work reveals potential evolutionary trajectories by which cells can maintain functional mitochondria, as well as the physiological implications of such adaptations.
Keywords: experimental evolution, mitochondrial DNA, mitochondrial quality control, replicative lifespan, yeast
Suggested Citation: Suggested Citation