Format

Send to

Choose Destination
Cell. 2015 Jan 15;160(1-2):132-44. doi: 10.1016/j.cell.2014.11.048. Epub 2014 Dec 23.

Endogenous hydrogen sulfide production is essential for dietary restriction benefits.

Author information

1
Department of Genetics and Complex Diseases, Harvard School of Public Health, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
2
Institute for Molecular Biosciences, NAWI Graz, University of Graz, Graz 8010, Austria.
3
Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
4
Department of Genetics and Complex Diseases, Harvard School of Public Health, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Surgery and the Heart and Vascular Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
5
Department of Surgery and the Heart and Vascular Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
6
Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada.
7
Institute for Molecular Biosciences, NAWI Graz, University of Graz, Graz 8010, Austria; BioTechMed Graz, Humboldtstrasse 50, Graz 8010, Austria.
8
Department of Genetics and Complex Diseases, Harvard School of Public Health, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: jmitchel@hsph.harvard.edu.

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.

PMID:
25542313
PMCID:
PMC4297538
DOI:
10.1016/j.cell.2014.11.048
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center