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S-nitrosylation drives cell senescence and aging in mammals by controlling mitochondrial dynamics and mitophagy.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 4/10/2018, Vol. 115 Issue 15, pE3388-3397. 10p. - Publication Year :
- 2018
-
Abstract
- S-nitrosylation, a prototypic redox-based posttranslational modification, is frequently dysregulated in disease. S-nitrosoglutathione reductase (GSNOR) regulates protein S-nitrosylation by functioning as a protein denitrosylase. Deficiency of GSNOR results in tumorigenesis and disrupts cellular homeostasis broadly, including metabolic, cardiovascular, and immune function. Here, we demonstrate that GSNOR expression decreases in primary cells undergoing senescence, as well as in mice and humans during their life span. In stark contrast, exceptionally long-lived individuals maintain GSNOR levels. We also show that GSNOR deficiency promotes mitochondrial nitrosative stress, including excessive S-nitrosylation of Drp1 and Parkin, thereby impairing mitochondrial dynamics and mitophagy. Our findings implicate GSNOR in mammalian longevity, suggest a molecular link between protein S-nitrosylation and mitochondria quality control in aging, and provide a redoxbased perspective on aging with direct therapeutic implications. [ABSTRACT FROM AUTHOR]
- Subjects :
- *NITROSYLATION
*OXIDATIVE stress
*CELLULAR aging
*GENE expression
*MITOCHONDRIA
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 115
- Issue :
- 15
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 129109261
- Full Text :
- https://doi.org/10.1073/pnas.1722452115