Mechanisms by which different functional states of mitochondria define yeast longevity.

Adam Beach,Vladimir Titorenko,Anthony Arlia-Ciommo,Anna Leonov,Veronika Svistkova,Vicky Lutchman

doi:10.3390/ijms16035528

Adam Beach, Vladimir Titorenko + Show 4 more

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https://doi.org/10.3390/ijms16035528

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Abstract

Mitochondrial functionality is vital to organismal physiology. A body of evidence supports the notion that an age-related progressive decline in mitochondrial function is a hallmark of cellular and organismal aging in evolutionarily distant eukaryotes. Studies of the baker’s yeast Saccharomyces cerevisiae, a unicellular eukaryote, have led to discoveries of genes, signaling pathways and chemical compounds that modulate longevity-defining cellular processes in eukaryotic organisms across phyla. These studies have provided deep insights into mechanistic links that exist between different traits of mitochondrial functionality and cellular aging. The molecular mechanisms underlying the essential role of mitochondria as signaling organelles in yeast aging have begun to emerge. In this review, we discuss recent progress in understanding mechanisms by which different functional states of mitochondria define yeast longevity, outline the most important unanswered questions and suggest directions for future research.

Highlights

The functional state of mitochondria is crucial for organismal physiology in all eukaryotes [1,2,3,4,5]
Rtg2 is essential for reducing the rate of yeast replicative aging because this protein (1) triggers the mitochondrial retrograde signaling pathway by stimulating nuclear import of the Rtg1-Rtg3 heterodimeric transcription factor; this factor orchestrates an anti-aging transcriptional program by activating expression of many nuclear genes involved in carbohydrate and nitrogen metabolism, peroxisomal fatty acid oxidation and anaplerotic reactions, peroxisome proliferation, stabilization of nuclear and mitochondrial genomes, and stress response [136,138,164]; and (2) is imported into the nucleus, where it increases genome stability and slows down the synthesis of extrachromosomal rDNA circles known to be one of the “aging factors” limiting the replicative lifespan of the mother cell [136,138,164] (Figure 2A)
A culture of chronologically aging yeast in a liquid medium progresses through a series of critical lifespan periods that define its longevity; we have recently proposed to use the term “lifespan checkpoint” for describing each of these consecutive periods of yeast chronological lifespan [18,19,20,145,184]