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SLC25A39, a mitochondrial transporter, maintains the mitochondrial homeostasis. This study investigated the role of SLC25A39 in the Cd-induced disruption of mitochondrial homeostasis in rat neuronal cells. The results revealed that Cd exposure markedly upregulated the SLC25A39 protein levels in neuronal cells. SLC25A39 deficiency further aggravated Cd-induced mitochondrial oxidative-stress-related abnormalities, including mitochondrial glutathione (mtGSH) depletion, elevated lipid peroxidation, mitochondrial reactive oxygen species (mtROS) accumulation, and reduced mitochondrial SOD2 protein levels. Moreover, SLC25A39 deficiency aggravated Cd-induced mitochondrial dysfunction, suppressed biogenesis, disrupted the dynamic balance, and hyperactivated mitophagy. Notably, DRP1 inhibition suppressed the Cd-induced upregulation of Pink1 and Parkin in SLC25A39-deficient PC12 cells. Collectively, SLC25A39 confers resistance to Cd-induced pleiotropic mitochondrial injuries, including oxidative stress, dysfunction, impaired biogenesis, dynamic imbalance, and excessive mitophagy. In PC12 cells, SLC25A39 may limit excessive mitophagy by negatively regulating the DRP1 activity.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c05935","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:02:00Z","timestamp":1787032920000},"page":"26699-26713","source":"Crossref","is-referenced-by-count":0,"title":["SLC25A39: A Guardian against Cadmium-Induced Pleiotropic\nDisruption of Mitochondrial Homeostasis in Rat Neuronal Cells"],"prefix":"10.1021","volume":"74","author":[{"given":"Li","family":"Wang","sequence":"first","affiliation":[{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]},{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Xuzhou Vocational College of Bioengineering , , , ,","place":["Xuzhou, Jiangsu, China, 221006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianzu","family":"Luo","sequence":"additional","affiliation":[{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]},{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhua","family":"Yao","sequence":"additional","affiliation":[{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]},{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8108-0723","authenticated-orcid":true,"given":"Yonggang","family":"Ma","sequence":"additional","affiliation":[{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]},{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2507-4749","authenticated-orcid":true,"given":"Xishuai","family":"Tong","sequence":"additional","affiliation":[{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]},{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2637-3895","authenticated-orcid":true,"given":"Hui","family":"Zou","sequence":"additional","affiliation":[{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]},{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhong","family":"Gu","sequence":"additional","affiliation":[{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]},{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuezhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]},{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8023-0751","authenticated-orcid":true,"given":"Jianchun","family":"Bian","sequence":"additional","affiliation":[{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]},{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9071-8363","authenticated-orcid":true,"given":"Zongping","family":"Liu","sequence":"additional","affiliation":[{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]},{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9612-2750","authenticated-orcid":true,"given":"Yan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]},{"name":"Yangzhou University , , , ,","place":["Yangzhou, Jiangsu, China, 225009"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"2026090104482038700_cit1","doi-asserted-by":"publisher","first-page":"898034","DOI":"10.1155\/2013\/898034","article-title":"Cadmium and its neurotoxic\neffects","volume":"2013","author":"Wang","year":"2013","journal-title":"Oxid. 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