Autophagy extends lifespan via vacuolar acidification

Microbial Cell

Christoph Magnes¹  Thomas R. Pieber¹  Frank Sinner¹  Guillermo Marino²  Guido Kroemer²  Rafal Koziel³  Pidder Jansen-Dürr³  Ivan Hajnal⁴  Lisa Klug⁴  Iryna Entfellner⁴  Sabrina Büttner⁴  Didac Carmona-Gutierrez⁴  Frank Madeo⁴  Christine Netzberger⁴  Kai-Uwe Fröhlich⁴  Slaven Stekovic⁴  Christian Schmid⁴  Tobias Eisenberg⁴  Thomas Kickenweiz⁴  Christoph Ruckenstuhl⁴  Christina Gleixner⁴  Alice G. Sorgo⁴ 

[1] HEALTH-Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H., 8010 Graz, Austria.;INSERM, U848, F-94805 Villejuif, France.;Institute for Biomedical Aging Research (IBA), Austrian Academy of Sciences, 6020 Innsbruck, Austria.;Institute for Molecular Biosciences, University of Graz, 8010 Graz, Austria.;

关键词: autophagy;    methionine restriction;    longevity;    chronological lifespan;    dietary restriction;    vacuole;    lysosome;    acidification;   

DOI  :  10.15698/mic2014.05.147

来源: DOAJ

【 摘 要 】

Methionine restriction (MetR) is one of the rare regimes that prolongs lifespan across species barriers. Using a yeast model, we recently demonstrated that this lifespan extension is promoted by autophagy, which in turn requires vacuolar acidification. Our study is the first to place autophagy as one of the major players required for MetR-mediated longevity. In addition, our work identifies vacuolar acidification as a key downstream element of autophagy induction under MetR, and possibly after rapamycin treatment. Unlike other amino acids, methionine plays pleiotropic roles in many metabolism-relevant pathways. For instance, methionine (i) is the N-terminal amino acid of every newly translated protein; (ii) acts as the central donor of methyl groups through S-adenosyl methionine (SAM) during methylation reactions of proteins, DNA or RNA; and (iii) provides the sulfhydryl groups for FeS-cluster formation and redox detoxification via transsulfuration to cysteine. Intriguingly, MetR causes lifespan extension, both in yeast and in rodents. We could show that in Saccharomyces cerevisiae, chronological lifespan (CLS) is increased in two specific methionine-auxotrophic strains (namely Δmet2 and Δmet15).

【 授权许可】

Unknown