Denitrosylate and live longer: how ADH5/GSNOR links mitophagy to aging

Autophagy
Salvatore Rizza, Giuseppe Filomeni

Abstract

Mitochondrial dynamics is required to adapt the manifold functions of mitochondria to cell needs and regulate their turnover by mitophagy. Actually, only if fragmented, mitochondria are engulfed by phagophores, the precursors to autophagosomes, and subsequently degraded. This process is essential to maintain a correct and healthy number of mitochondria that, otherwise, might be harmful. They, indeed, represent the main source of reactive oxygen species that - according to the mitochondrial free radical theory of aging - can cause aging when chronically overproduced. In a recent study, we demonstrated that S-nitrosylation, the reversible modification of cysteine residues by nitric oxide (NO), hyperactivates mitochondrial fragmentation by targeting DNM1L/Drp1 (dynamin 1-like) at Cys644, but inhibits mitophagy, the concomitant occurrence of these conditions driving cell senescence. We demonstrated that cell senescence, as well as mouse and human aging are characterized by an epigenetically-driven decrease in ADH5/GSNOR (alcohol dehydrogenase 5 [class III], chi polypeptide), suggesting that ADH5 may act as new longevity gene.

References

Mar 28, 2018·Proceedings of the National Academy of Sciences of the United States of America·Salvatore RizzaGiuseppe Filomeni

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Citations

Jul 13, 2019·Rejuvenation Research·Andrew Mendelsohn, James Larrick
Jan 15, 2020·Antioxidants & Redox Signaling·Costanza MontagnaGiuseppe Filomeni
Sep 21, 2018·Frontiers in Oncology·Salvatore Rizza, Giuseppe Filomeni
Nov 30, 2019·Oxidative Medicine and Cellular Longevity·Ne N WuJun Ren
May 16, 2020·Frontiers in Physiology·Fiorella FaienzaGiuseppe Filomeni
Dec 3, 2020·International Journal of Molecular Sciences·Daniele CapitanioCecilia Gelfi
Mar 1, 2020·Biochemical Pharmacology·Salvatore RizzaGiuseppe Filomeni
Jun 27, 2021·Archives of Biochemistry and Biophysics·Mariarosaria D'ErricoEugenia Dogliotti
Aug 26, 2021·Nature Reviews. Molecular Cell Biology·Ji-Hoon Lee, Tanya T Paull

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Methods Mentioned

BETA
transgenic
confocal microscopy
GTPase
fluorescence microscopy
ubiquitination

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