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

doi:10.1016/j.cell.2014.11.048

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

Research output: Contribution to journal › Article

208 Citations (Scopus)

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

Original language	English
Pages (from-to)	132-144
Number of pages	13
Journal	Cell
Volume	160
Issue number	1-2
DOIs	https://doi.org/10.1016/j.cell.2014.11.048
Publication status	Published - 2015 Jan 15
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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Hine, C., Harputlugil, E., Zhang, Y., Ruckenstuhl, C., Lee, B. C., Brace, L., Longchamp, A., Treviño-Villarreal, J. H., Mejia, P., Ozaki, C. K., Wang, R., Gladyshev, V. N., Madeo, F., Mair, W. B., & Mitchell, J. R. (2015). Endogenous hydrogen sulfide production is essential for dietary restriction benefits. Cell, 160(1-2), 132-144. https://doi.org/10.1016/j.cell.2014.11.048

Endogenous hydrogen sulfide production is essential for dietary restriction benefits. / Hine, Christopher; Harputlugil, Eylul; Zhang, Yue; Ruckenstuhl, Christoph; Lee, Byung Cheon; Brace, Lear; Longchamp, Alban; Treviño-Villarreal, Jose H.; Mejia, Pedro; Ozaki, C. Keith; Wang, Rui; Gladyshev, Vadim N.; Madeo, Frank; Mair, William B.; Mitchell, James R.

In: Cell, Vol. 160, No. 1-2, 15.01.2015, p. 132-144.

Research output: Contribution to journal › Article

Hine, Christopher ; Harputlugil, Eylul ; Zhang, Yue ; Ruckenstuhl, Christoph ; Lee, Byung Cheon ; Brace, Lear ; Longchamp, Alban ; Treviño-Villarreal, Jose H. ; Mejia, Pedro ; Ozaki, C. Keith ; Wang, Rui ; Gladyshev, Vadim N. ; Madeo, Frank ; Mair, William B. ; Mitchell, James R. / Endogenous hydrogen sulfide production is essential for dietary restriction benefits. In: Cell. 2015 ; Vol. 160, No. 1-2. pp. 132-144.

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