{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:20:23Z","timestamp":1788826823182,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:00:00Z","timestamp":1699488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Radiation\u2010induced heart damage caused by low\u2010dose X\u2010rays has a significant impact on tumour patients' prognosis, with cardiac hypertrophy being the most severe noncarcinogenic adverse effect. Our previous study demonstrated that mitophagy activation promoted cardiac hypertrophy, but the underlying mechanisms remained unclear. In the present study, PARL\u2010IN\u20101 enhanced excessive hypertrophy of cardiomyocytes and exacerbated mitochondrial damage.\u00a0Isobaric tags for relative and absolute quantification\u2010based quantitative proteomics identified NDP52 as a crucial target mediating cardiac hypertrophy induced by low\u2010dose X\u2010rays. SUMOylation proteomics revealed that the SUMO E3 ligase MUL1 facilitated NDP52 SUMOylation through SUMO2. Co\u2010IP coupled with LC\u2013MS\/MS identified a critical lysine residue at position 262 of NDP52 as the key site for SUMO2\u2010mediated SUMOylation of NDP52. The point mutation plasmid NDP52\n                    <jats:sup>K262R<\/jats:sup>\n                    inhibited mitophagy under MUL1 overexpression, as evidenced by inhibition of LC3 interaction with NDP52, PINK1 and LAMP2A. A mitochondrial dissociation study revealed that NDP52\n                    <jats:sup>K262R<\/jats:sup>\n                    inhibited PINK1 targeting to endosomes early endosomal marker (EEA1), late\/lysosome endosomal marker (LAMP2A) and recycling endosomal marker (RAB11), and laser confocal microscopy confirmed that NDP52\n                    <jats:sup>K262R<\/jats:sup>\n                    impaired the recruitment of mitochondria to the autophagic pathway through EEA1\/RAB11 and ATG3, ATG5, ATG16L1\u00a0and STX17, but did not affect mitochondrial delivery to lysosomes via LAMP2A for degradation. In conclusion, our findings suggest that MUL1\u2010mediated SUMOylation of NDP52 plays a crucial role in regulating mitophagy in the context of low\u2010dose X\u2010ray\u2010induced cardiac hypertrophy. Two hundred sixty\u2010second\u00a0lysine of NDP52 is identified as a key SUMOylation site for low\u2010dose X\u2010ray promoting mitophagy activation and cardiac hypertrophy. Collectively, this study provides novel implications for the development of therapeutic strategies aimed at preventing the progression of cardiac hypertrophy induced by low\u2010dose X\u2010rays.\n                  <\/jats:p>","DOI":"10.1002\/jcp.31145","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T04:47:33Z","timestamp":1699505253000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["NDP52 SUMOylation contributes to low\u2010dose X\u2010rays\u2010induced cardiac hypertrophy through PINK1\/Parkin\u2010mediated mitophagy via MUL1\/SUMO2 signalling"],"prefix":"10.1002","volume":"239","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6564-3495","authenticated-orcid":false,"given":"Anbo","family":"Gao","sequence":"first","affiliation":[{"name":"Hengyang Medical School,\u00a0Clinical Research Institute, The Second Affiliated Hospital University of South China Hengyang Hunan 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