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Parthenolide (PTL), a sesquiterpene lactone found in large amounts in the leaves of feverfew, possesses anti\u2010inflammatory, anti\u2010migraine, and anticancer properties. Although PTL was reported to alleviate cancer cachexia and improve skeletal muscle characteristics in a cancer cachexia model, its actions on oxidative stress\u2010induced damage in C2C12 myoblasts have not been reported and the regulatory mechanisms have not yet been defined. In our study, PTL attenuated H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced growth inhibition and morphological changes. Furthermore, PTL exhibited scavenging activity against reactive oxygen species and protected C2C12 cells from apoptosis in response to H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>. Meanwhile, PTL suppressed collapse of the mitochondrial membrane potential, thereby contributing to normalizing H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced autophagy flux and mitophagy, correlating with inhibiting degradation of mitochondrial marker protein TIM23, the increase in LC3\u2010II expression and the reduction of mitochondria DNA. Besides its protective effect on mitochondria, PTL also prevented H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010induced lysosomes damage in C2C12 cells. In addition, the phosphorylation of p53, cathepsin B, and Bax\/Bcl\u20102 protein levels, and the translocation of Bax from the cytosol to mitochondria induced by H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> in C2C12 cells was significantly reduced by PTL. In conclusion, PTL modulates oxidative stress\u2010induced mitophagy and protects C2C12 myoblasts against apoptosis, suggesting a potential protective effect against oxidative stress\u2010associated skeletal muscle diseases.<\/jats:p>","DOI":"10.1002\/jcb.28839","type":"journal-article","created":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T04:15:01Z","timestamp":1559189701000},"page":"15695-15708","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Parthenolide regulates oxidative stress\u2010induced mitophagy and suppresses apoptosis through p53 signaling pathway in C2C12 myoblasts"],"prefix":"10.1002","volume":"120","author":[{"given":"Yinghui","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China Tianjin Medical University Tianjin China"},{"name":"Tianjin Key Laboratory of Lung Cancer 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