Endogenous Hydrogen Sulfide Production Is Essential for Dietary Restriction Benefits | Zendy

Christopher Hine | Zendy; Eylul Harputlugil | Zendy; Yue Zhang | Zendy; Christoph Ruckenstuhl | Zendy; Byung Cheon Lee | Zendy; Lear E. Brace | Zendy; Alban Longchamp | Zendy; J. Humberto Treviño-Villarreal | Zendy; Pedro Mejia | Zendy; C. Keith Ozaki | Zendy; Rui Wang | Zendy; Vadim N. Gladyshev | Zendy; Frank Madeo | Zendy; William B. Mair | Zendy; James R. Mitchell | Zendy

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Endogenous Hydrogen Sulfide Production Is Essential for Dietary Restriction Benefits

Author(s) -

Christopher Hine,

Eylul Harputlugil,

Yue Zhang,

Christoph Ruckenstuhl,

Byung Cheon Lee,

Lear E. Brace,

Alban Longchamp,

J. Humberto Treviño-Villarreal,

Pedro Mejia,

C. Keith Ozaki,

Rui Wang,

Vadim N. Gladyshev,

Frank Madeo,

William B. Mair,

James R. Mitchell

Publication year - 2014

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2014.11.048

Subject(s) - biology , cystathionine beta synthase , longevity , hydrogen sulfide , cystathionine gamma lyase , biochemistry , enzyme , genetics , amino acid , sulfur , microbiology and biotechnology , methionine , chemistry , organic chemistry

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:

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