{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:36:03Z","timestamp":1791909363024,"version":"4.3.4"},"reference-count":72,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,1,15]],"date-time":"2023-01-15T00:00:00Z","timestamp":1673740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073523"],"award-info":[{"award-number":["82073523"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Cadmium (Cd) is a high\u2010risk pathogenic toxin for hepatic diseases. Excessive mitophagy is a hallmark in Cd\u2010induced hepatotoxicity. However, the underlying mechanism remains obscure. Mitochondrial calcium uniporter (MCU) is a key regulator for mitochondrial and cellular homeostasis. Here, Cd exposure upregulated MCU expression and increased mitochondrial Ca\n                    <jats:sup>2+<\/jats:sup>\n                    uptake are found. MCU inhibition through siRNA or by Ru360 significantly attenuates Cd\u2010induced excessive mitophagy, thereby rescues mitochondrial dysfunction and increases hepatocyte viability. Heterozygous MCU knockout mice exhibit improved liver function, ameliorated pathological damage, less mitochondrial fragmentation, and mitophagy after Cd exposure. Mechanistically, Cd upregulates MCU expression through phosphorylation activation of cAMP\u2010response element binding protein at Ser133(CREB\n                    <jats:sup>S133<\/jats:sup>\n                    ) and subsequent binding of MCU promoter at the TGAGGTCT, ACGTCA, and CTCCGTGATGTA regions, leading to increased MCU gene transcription. The upregulated MCU intensively interacts with voltage\u2010dependent anion\u2010selective channel protein 1 (VDAC1), enhances its dimerization and ubiquitination, resulting in excessive mitophagy. This study reveals a novel mechanism, through which Cd upregulates MCU to enhance mitophagy and hepatotoxicity.\n                  <\/jats:p>","DOI":"10.1002\/advs.202203869","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T00:07:36Z","timestamp":1673827656000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["MCU Upregulation Overactivates Mitophagy by Promoting VDAC1 Dimerization and Ubiquitination in the Hepatotoxicity of Cadmium"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7658-7739","authenticated-orcid":false,"given":"Cong","family":"Liu","sequence":"first","affiliation":[{"name":"Chongqing Key Laboratory of Prevention and Treatment for Occupational Diseases and Poisoning  Chongqing 400060 P. R. 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