Mitophagy switches cell death from apoptosis to necrosis in NSCLC cells treated with oncolytic measles virus
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Mao Xia1, Gang Meng1, Aiqin Jiang1, Aiping Chen1, Meike Dahlhaus3, Patrick Gonzalez4, Christian Beltinger3, Jiwu Wei1, 2
1 Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
2 Nanjing University Hightech Institute at Suzhou, Suzhou, China
3 Dept. of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany
4 Inserm U785, Centre hepato-biliaire, Hopital Paul Brousse, Villejuif, France
Jiwu Wei, email:
Keywords: oncolytic measles virus; non-small cell lung cancer; autophagy; mitophagy; apoptosis; necrosis
Received: March 27, 2014 Accepted: May 27, 2014 Published: May 28, 2014
Although apoptotic phenomena have been observed in malignant cells infected by measles virus vaccine strain Edmonston B (MV-Edm), the precise oncolytic mechanisms are poorly defined. In this study we found that MV-Edm induced autophagy and sequestosome 1-mediated mitophagy leading to decreased cytochrome c release, which blocked the pro-apoptotic cascade in non-small cell lung cancer cells (NSCLCs). The decrease of apoptosis by mitophagy favored viral replication. Persistent viral replication sustained by autophagy ultimately resulted in necrotic cell death due to ATP depletion. Importantly, when autophagy was impaired in NSCLCs MV-Edm-induced cell death was significantly abrogated despite of increased apoptosis. Taken together, our results define a novel oncolytic mechanism by which mitophagy switches cell death from apoptosis to more efficient necrosis in NSCLCs following MV-Edm infection. This provides a foundation for future improvement of oncolytic virotherapy or antiviral therapy.
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