| Literature DB >> 25542313 |
Christopher Hine1, Eylul Harputlugil1, Yue Zhang1, Christoph Ruckenstuhl2, Byung Cheon Lee3, Lear Brace1, Alban Longchamp4, Jose H Treviño-Villarreal1, Pedro Mejia1, C Keith Ozaki5, Rui Wang6, Vadim N Gladyshev3, Frank Madeo7, William B Mair1, James R Mitchell8.
Abstract
Dietary restriction (DR) without malnutrition encompasses numerous regimens with overlapping benefits including longevity and stress resistance, but unifying nutritional and molecular mechanisms remain elusive. In a mouse model of DR-mediated stress resistance, we found that sulfur amino acid (SAA) restriction increased expression of the transsulfuration pathway (TSP) enzyme cystathionine γ-lyase (CGL), resulting in increased hydrogen sulfide (H2S) production and protection from hepatic ischemia reperfusion injury. SAA supplementation, mTORC1 activation, or chemical/genetic CGL inhibition reduced H2S production and blocked DR-mediated stress resistance. In vitro, the mitochondrial protein SQR was required for H2S-mediated protection during nutrient/oxygen deprivation. Finally, TSP-dependent H2S production was observed in yeast, worm, fruit fly, and rodent models of DR-mediated longevity. Together, these data are consistent with evolutionary conservation of TSP-mediated H2S as a mediator of DR benefits with broad implications for clinical translation. PAPERFLICK:Entities:
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Year: 2014 PMID： 25542313 PMCID： PMC4297538 DOI： 10.1016/j.cell.2014.11.048
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582