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Experimental Evolution Improves Mitochondrial Genome Quality Control in Saccharomyces Cerevisiae and Extends Its Replicative Lifespan

28 Pages Posted: 24 Mar 2021 Publication Status: Published

See all articles by Ahmed A. A. Amine

Ahmed A. A. Amine

National Defence Medical Center - Graduate Institute of Life Science

Chia-Wei Liao

Academia Sinica - Institute of Molecular Biology

Po-Chen Hsu

Academia Sinica - Institute of Molecular Biology

Jun-Yi Leu

Academia Sinica - Institute of Molecular Biology

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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

Amine, Ahmed A. A. and Liao, Chia-Wei and Hsu, Po-Chen and Leu, Jun-Yi, Experimental Evolution Improves Mitochondrial Genome Quality Control in Saccharomyces Cerevisiae and Extends Its Replicative Lifespan. Available at SSRN: https://ssrn.com/abstract=3811875 or http://dx.doi.org/10.2139/ssrn.3811875
This version of the paper has not been formally peer reviewed.

Ahmed A. A. Amine

National Defence Medical Center - Graduate Institute of Life Science ( email )

Taiwan

Chia-Wei Liao

Academia Sinica - Institute of Molecular Biology ( email )

128 Academia Road, Section 2
Taipei, Nangang 11529
Taiwan

Po-Chen Hsu

Academia Sinica - Institute of Molecular Biology ( email )

128 Academia Road, Section 2
Taipei, Nangang 11529
Taiwan

Jun-Yi Leu (Contact Author)

Academia Sinica - Institute of Molecular Biology ( email )

128 Academia Road, Section 2
Taipei, Nangang 11529
Taiwan

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