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 | |
| Publication status | Published - 2015 Jan 15 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
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
}
TY - JOUR
T1 - Endogenous hydrogen sulfide production is essential for dietary restriction benefits
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. PaperFlick
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. PaperFlick
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U2 - 10.1016/j.cell.2014.11.048
DO - 10.1016/j.cell.2014.11.048
M3 - Article
C2 - 25542313
AN - SCOPUS:84920995923
VL - 160
SP - 132
EP - 144
JO - Cell
JF - Cell
SN - 0092-8674
IS - 1-2
ER -