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ROS control biological adaptation through reversible oxidation of protein cysteines, yet the targets of DR-initiated redox signaling are unknown. Here we generate OxiDR, a tissue-resolved atlas of the cysteine redox proteome that quantifies oxidation state under DR. Rather than oxidizing the proteome broadly, DR selectively targets a high-amplitude set of cysteines in a tissue-specific manner, allowing systematic classification of biological processes subject to DR-mediated redox regulation. Among the cysteines most highly oxidized upon DR is Cys19 of the core autophagy protein ATG5. We show oxidation of Cys19 is required for ATG5-mediated autophagosome formation and for autophagy triggered by nutrient restriction in human cells and mice. Reversible oxidation of this cysteine promotes ATG5 binding to ATG10, thus forming the ATG5\u2013ATG12 conjugate that lipidates LC3B\/ATG8 and matures the autophagosome. In mice, loss of this redox switch prevents effective initiation of autophagy upon nutrient restriction, resulting in gross tissue pathology and rapid onset of mortality. The autophagic response to nutrient restriction is thus gated by oxidation of a single cysteine.<\/jats:p>","DOI":"10.64898\/2026.09.23.753803","type":"posted-content","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:30:16Z","timestamp":1790274616000},"source":"Crossref","is-referenced-by-count":0,"title":["Redox activation of ATG5 licenses autophagy upon nutrient restriction"],"prefix":"10.64898","author":[{"given":"Sanghee","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Cancer Biology, Dana\u2013Farber Cancer Institute, Boston, MA, USA"},{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina D.","family":"Korobkina","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Dana\u2013Farber Cancer Institute, Boston, MA, USA"},{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Lennicke","sequence":"additional","affiliation":[{"name":"MRC Laboratory of Medical Science (LMS), London, UK"},{"name":"Institute of Clinical Sciences, Imperial College London, Hammersmith Hospital Campus, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Burger","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Dana\u2013Farber Cancer Institute, Boston, MA, USA"},{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingsen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Dana\u2013Farber Cancer Institute, Boston, MA, USA"},{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haopeng","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Dana\u2013Farber Cancer Institute, Boston, MA, USA"},{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA, USA"},{"name":"Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA"},{"name":"Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Dana\u2013Farber Cancer Institute, Boston, MA, USA"},{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan J.","family":"Petrocelli","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Dana\u2013Farber Cancer Institute, Boston, MA, USA"},{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelley M.","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Dana\u2013Farber Cancer Institute, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Dana\u2013Farber Cancer Institute, Boston, MA, USA"},{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Dana\u2013Farber Cancer Institute, Boston, MA, USA"},{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Dana\u2013Farber Cancer Institute, Boston, MA, USA"},{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C.","family":"Perez-Matos","sequence":"additional","affiliation":[{"name":"Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muneeb A.","family":"Sharif","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Dana\u2013Farber Cancer Institute, Boston, MA, USA"},{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuchun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena M.","family":"Cochem\u00e9","sequence":"additional","affiliation":[{"name":"MRC Laboratory of Medical Science (LMS), London, UK"},{"name":"Institute of Clinical Sciences, Imperial College London, Hammersmith Hospital Campus, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William B.","family":"Mair","sequence":"additional","affiliation":[{"name":"Department of Molecular Metabolism, Harvard T.H. 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