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Here, we identify a non-canonical SUMO-2\/3 modification of PINK1 that suppresses basal mitophagy. We show that the mitochondrial E3 ligase mitochondrial-anchored protein ligase (MAPL\/MUL1) promotes PINK1 SUMO-2\/3 modification, while MAPL depletion reduces SUMOylation and enhances basal mitophagy. Targeted deSUMOylation increases PINK1 stabilisation and augments mitophagy. These findings reveal a novel SUMO-based checkpoint for basal PINK1 activation and mitochondrial quality control.<\/jats:p>","DOI":"10.1101\/2025.05.27.656300","type":"posted-content","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T05:15:14Z","timestamp":1748495714000},"source":"Crossref","is-referenced-by-count":0,"title":["SUMO-2\/3 modification of PINK1 restrains basal mitophagy through MAPL-dependent regulation of mitochondrial surveillance"],"prefix":"10.64898","author":[{"given":"Nitheyaa Shree","family":"Ramesh","sequence":"first","affiliation":[{"name":"Centre for Synaptic Plasticity, School of Biochemistry, Biomedical Sciences Building, University of Bristol, University Walk, Bristol, BS8 1TD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Seager","sequence":"additional","affiliation":[{"name":"Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University of Bristol, University Walk, Bristol, BS8 1TD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8115-8592","authenticated-orcid":false,"given":"Kevin A.","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Centre for Synaptic Plasticity, School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University of Bristol, University Walk, Bristol, BS8 1TD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3589-8335","authenticated-orcid":false,"given":"Jeremy M.","family":"Henley","sequence":"additional","affiliation":[{"name":"Centre for Synaptic Plasticity, School of Biochemistry, Biomedical Sciences Building, University of Bristol, University Walk, Bristol, BS8 1TD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041123540139000_2025.05.27.656300v2.1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.620906"},{"key":"2026041123540139000_2025.05.27.656300v2.2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0500617102"},{"key":"2026041123540139000_2025.05.27.656300v2.3","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2009.86"},{"key":"2026041123540139000_2025.05.27.656300v2.4","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15319"},{"issue":"2","key":"2026041123540139000_2025.05.27.656300v2.5","first-page":"e00254","article-title":"SUMO-modified FADD recruits cytosolic Drp1 and caspase-10 to mitochondria for regulated necrosis","volume":"37","year":"2017","journal-title":"Molecular and Cellular Biology"},{"key":"2026041123540139000_2025.05.27.656300v2.6","doi-asserted-by":"crossref","unstructured":"Cilenti, L. , Di Gregorio, J. , Mahar, R. , Liu, F. , Ambivero, C. 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