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KMID : 1034820190150010065
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Molecular & Cellular Toxicology
2019 Volume.15 No. 1 p.65 ~ p.73
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Chronological lifespan regulation of Saccharomyces cerevisiae by leucine biosynthesis pathway genes via TOR1 and COX2 expression regulation
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Gorospe Choco Michael
Yu Sung-Lim
Kang Mi-Sun
Lee Sung-Keun
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Abstract
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Backgrounds: Leucine is involved in various cellular mechanisms, including protein metabolism, insulin signaling, and longevity control. Nevertheless, the contribution of leucine metabolism genes to longevity have not been thoroughly studied.
Methods: Several mutants of leucine biosynthesis genes were constructed, and their effect on yeast lifespan and various phenotypes were examined.
Results: Several deletion mutants increase yeast lifespan. Among those, LEU2 and leu4Δ cells exhibit significantly increased lifespan, moderately increased reactive oxygen species (ROS) generation, decreased Tor1p expression, significantly increased expression of a cytochrome c oxidase subunit, and decreased cell death. In these cells, reduced Tor1p seemed to stimulate a slight increase in ROS generation which stimulates Cox2p expression that can prevent cellular damage. Indeed, the rate of cell death of LEU2 and leu4Δ cells was drastically decreased.
Conclusion: LEU2 and LEU4 seem critical in determining yeast lifespan by providing a hormetic effect that promotes yeast longevity.
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KEYWORD
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Yeast, Leucine, LEU2, LEU4, Chronological lifespan
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