Journal
AGING-US
Volume 11, Issue 12, Pages 4254-4273Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.102050
Keywords
high-throughput genetic screening; methionine restriction; hydrogen sulfide; sulfate assimilation; reactive oxygen species
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Funding
- National Research Foundation of Korea (NRF) - Korean government (Ministry of Science, ICT & Future Planning) [2018R1A1A1 A05079386, 2018M3A9F3055925]
- Korea University Future Research Grant
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Endogenously produced hydrogen sulfide was proposed to be an underlying mechanism of lifespan extension via methionine restriction. However, hydrogen sulfide regulation and its beneficial effects via methionine restriction remain elusive. Here, we identified the genes required to increase hydrogen sulfide production under methionine restriction condition using genome-wide high-throughput screening in yeast strains with single-gene deletions. Sulfate assimilation-related genes, such as MET1, MET3, MET5, and MET10, were found to be particularly crucial for hydrogen sulfide production. Interestingly, methionine restriction failed to increase hydrogen sulfide production in mutant strains; however, it successfully extended chronological lifespan and reduced reactive oxygen species levels. Altogether, our observations suggested that increased hydrogen sulfide production via methionine restriction is not the mechanism underlying extended yeast lifespan, even though increased hydrogen sulfide production occurred simultaneously with yeast lifespan extension under methionine restriction condition.
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