S-Nitrosylation Drives Cell Senescence and Aging in Mammals By
S-nitrosylation drives cell senescence and aging in PNAS PLUS mammals by controlling mitochondrial dynamics and mitophagy Salvatore Rizzaa,1, Simone Cardacib,1, Costanza Montagnaa,c,1, Giuseppina Di Giacomod,2, Daniela De Zioa, Matteo Bordid, Emiliano Maiania, Silvia Campellod,e, Antonella Borrecaf, Annibale A. Pucag,h, Jonathan S. Stamleri,j, Francesco Cecconia,d,k, and Giuseppe Filomenia,d,3 aDanish Cancer Society Research Center, Center for Autophagy, Recycling and Disease, 2100 Copenhagen, Denmark; bDivision of Genetics and Cell Biology, Institute for Research and Health Care San Raffaele (IRCCS) Scientific Institute, 20132 Milan, Italy; cInstitute of Sports Medicine Copenhagen, Bispebjerg Hospital, 2400 Copenhagen, Denmark; dDepartment of Biology, Tor Vergata University, 00133 Rome, Italy; eIRCCS Fondazione Santa Lucia, 00146 Rome, Italy; fInstitute of Cellular Biology and Neuroscience, National Research Council, 00143 Rome, Italy; gCardiovascular Research Unit, IRCCS Multimedica, 20138 Milan, Italy; hDipartimento di Medicina e Chirurgia, University of Salerno, 84084 Fisciano Salerno, Italy; iInstitute for Transformative Molecular Medicine, Case Western Reserve University, Cleveland, OH 44106; jHarrington Discovery Institute, University Hospitals Case Medical Center, Cleveland, OH 44106; and kDepartment of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children’s Hospital, 00146 Rome, Italy Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved March 1, 2018 (received for review January 9, 2018) S-nitrosylation, a prototypic redox-based posttranslational modifi- found in experimental models of aging, supporting the idea that cation, is frequently dysregulated in disease. S-nitrosoglutathione GSNOR preserves cellular function. reductase (GSNOR) regulates protein S-nitrosylation by function- The free radical theory of aging postulates that oxidative ing as a protein denitrosylase.
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