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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

478 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.

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

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 2 Zero Hunger

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology

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10.1016/j.cell.2014.11.048

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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

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title = "Endogenous hydrogen sulfide production is essential for dietary restriction benefits",

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.",

author = "Christopher Hine and Eylul Harputlugil and Yue Zhang and Christoph Ruckenstuhl and Lee, \{Byung Cheon\} and Lear Brace and Alban Longchamp and Trevi{\~n}o-Villarreal, \{Jose H.\} and Pedro Mejia and Ozaki, \{C. Keith\} and Rui Wang and Gladyshev, \{Vadim N.\} and Frank Madeo and Mair, \{William B.\} and Mitchell, \{James R.\}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = jan,

day = "15",

doi = "10.1016/j.cell.2014.11.048",

language = "English",

volume = "160",

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AU - Hine, Christopher

AU - Harputlugil, Eylul

AU - Zhang, Yue

AU - Ruckenstuhl, Christoph

AU - Lee, Byung Cheon

AU - Brace, Lear

AU - Longchamp, Alban

AU - Treviño-Villarreal, Jose H.

AU - Mejia, Pedro

AU - Ozaki, C. Keith

AU - Wang, Rui

AU - Gladyshev, Vadim N.

AU - Madeo, Frank

AU - Mair, William B.

AU - Mitchell, James R.

PY - 2015/1/15

Y1 - 2015/1/15

N2 - 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.

AB - 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.

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SN - 0092-8674

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EP - 144

JO - Cell

JF - Cell

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ER -

Endogenous hydrogen sulfide production is essential for dietary restriction benefits

Abstract

Bibliographical note

UN SDGs

ASJC Scopus subject areas

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