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Reciprocal interactions between mtDNA and lifespan control in budding yeast.


ABSTRACT: Loss of mitochondrial DNA (mtDNA) results in loss of mitochondrial respiratory activity, checkpoint-regulated inhibition of cell cycle progression, defects in growth, and nuclear genome instability. However, after several generations, yeast cells can adapt to the loss of mtDNA. During this adaptation, rho0 cells, which have no mtDNA, exhibit increased growth rates and nuclear genome stabilization. Here, we report that an immediate response to loss of mtDNA is a decrease in replicative lifespan (RLS). Moreover, we find that adapted rho0 cells bypass the mtDNA inheritance checkpoint, exhibit increased mitochondrial function, and undergo an increase in RLS as they adapt to the loss of mtDNA. Transcriptome analysis reveals that metabolic reprogramming to compensate for defects in mitochondrial function is an early event during adaptation and that up-regulation of stress response genes occurs later in the adaptation process. We also find that specific subtelomeric genes are silenced during adaptation to loss of mtDNA. Moreover, we find that deletion of SIR3, a subtelomeric gene silencing protein, inhibits silencing of subtelomeric genes associated with adaptation to loss of mtDNA, as well as adaptation-associated increases in mitochondrial function and RLS extension.

SUBMITTER: Garcia EJ 

PROVIDER: S-EPMC6857569 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Reciprocal interactions between mtDNA and lifespan control in budding yeast.

Garcia Enrique J EJ   de Jonge Janeska J JJ   Liao Pin-Chao PC   Stivison Elizabeth E   Sing Cierra N CN   Higuchi-Sanabria Ryo R   Boldogh Istvan R IR   Pon Liza A LA  

Molecular biology of the cell 20191010 24


Loss of mitochondrial DNA (mtDNA) results in loss of mitochondrial respiratory activity, checkpoint-regulated inhibition of cell cycle progression, defects in growth, and nuclear genome instability. However, after several generations, yeast cells can adapt to the loss of mtDNA. During this adaptation, rho<sup>0</sup> cells, which have no mtDNA, exhibit increased growth rates and nuclear genome stabilization. Here, we report that an immediate response to loss of mtDNA is a decrease in replicative  ...[more]

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