Endogenous hydrogen sulfide production is essential for dietary restriction benefits
Christopher Hine, Eylul Harputlugil, Yue Zhang, Christoph Ruckenstuhl, Byung Cheon Lee, Lear Brace, Alban Longchamp, Jose H Treviño-Villarreal, Pedro Mejia, C Keith Ozaki, Rui Wang, Vadim N Gladyshev, Frank Madeo, William B Mair, James R Mitchell, Christopher Hine, Eylul Harputlugil, Yue Zhang, Christoph Ruckenstuhl, Byung Cheon Lee, Lear Brace, Alban Longchamp, Jose H Treviño-Villarreal, Pedro Mejia, C Keith Ozaki, Rui Wang, Vadim N Gladyshev, Frank Madeo, William B Mair, James R Mitchell
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:
Conflict of interest statement
The authors claim no conflicts of interest.
Copyright © 2015 Elsevier Inc. All rights reserved.
Figures
Source: PubMed