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Mitochondria are the main source and primary target of cellular ROS. We hypothesized that curcumin would regulate cellular redox status and mitochondrial function, depending on cell sensitivity and\/or curcumin concentration in normal cells. We examined the differences between low and high concentrations of curcumin, with specific attention focused on ROS levels, mitochondrial function, and cell viability in mouse C2C12 myoblast under normal and simulated conditions of diabetes. Cells incubated with high concentrations of curcumin (10\u201350\u2009\u03bcM) resulted in decreased cell viability and sustained robust increases in ROS levels. Mechanistic studies showed that increased ROS levels in cells incubated with 20\u2009\u03bcM curcumin induced opening of mitochondrial permeability transition pores and subsequent release of cytochrome c, activation of caspases 9 and 3\/7, and apoptotic cell death. Low concentrations of curcumin (1\u20135\u2009\u03bcM) did not affect cell viability, but induced a mild increase in ROS levels, which peaked at 2\u2009hr after the treatment. Incubation with 5\u2009\u03bcM curcumin also induced ROS\u2010dependent increases in mitochondrial mass and membrane potential. Finally, pretreatment with 5\u2009\u03bcM curcumin prevented high glucose\u2010induced oxidative cell injury. Our study suggests that mitochondria respond differentially depending on curcumin concentration\u2010dependent induction of ROS. The end result is either cell protection or death. Curcumin may be an effective therapeutic target for diabetes and other mitochondrial diseases when used in low concentrations.<\/jats:p>","DOI":"10.1002\/jcp.27370","type":"journal-article","created":{"date-parts":[[2018,9,24]],"date-time":"2018-09-24T07:51:00Z","timestamp":1537775460000},"page":"6371-6381","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Curcumin induces concentration\u2010dependent alterations in mitochondrial function through ROS in C2C12 mouse myoblasts"],"prefix":"10.1002","volume":"234","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0236-015X","authenticated-orcid":false,"given":"Tianzheng","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Military and Emergency Medicine Consortium for Health and Military Performance, Uniformed Services University of the Health Sciences Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Dohl","sequence":"additional","affiliation":[{"name":"Department of Military and Emergency Medicine Consortium for Health and Military Performance, Uniformed Services University of the Health Sciences Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falicia","family":"Elenberg","sequence":"additional","affiliation":[{"name":"Department of Military and Emergency Medicine Consortium for Health and Military Performance, Uniformed Services University of the Health Sciences Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Military and Emergency Medicine Consortium for Health and Military Performance, Uniformed Services University of the Health Sciences Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Deuster","sequence":"additional","affiliation":[{"name":"Department of Military and Emergency Medicine Consortium for Health and Military Performance, Uniformed Services University of the Health Sciences Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,24]]},"reference":[{"key":"e_1_2_7_1_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-008-9143-2"},{"key":"e_1_2_7_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2008.05.003"},{"key":"e_1_2_7_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2005.05.005"},{"key":"e_1_2_7_1_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.137455"},{"key":"e_1_2_7_1_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00001.2015"},{"key":"e_1_2_7_1_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00139.2004"},{"issue":"4","key":"e_1_2_7_1_8_1","first-page":"2895","article-title":"Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high\u2010risk or pre\u2010malignant lesions","volume":"21","author":"Cheng A. 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