title: Mitophagy switches cell death from apoptosis to necrosis in NSCLC cells treated with oncolytic measles virus.
abstract: 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.
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Mao
authors.initials: M
authors.lastname: Xia
authors.forename: Gang
authors.initials: G
authors.lastname: Meng
authors.forename: Aiqin
authors.initials: A
authors.lastname: Jiang
authors.forename: Aiping
authors.initials: A
authors.lastname: Chen
authors.forename: Meike
authors.initials: M
authors.lastname: Dahlhaus
authors.forename: Patrick
authors.initials: P
authors.lastname: Gonzalez
authors.forename: Christian
authors.initials: C
authors.lastname: Beltinger
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China; Nanjing University Hightech Institute at Suzhou, Suzhou, China.
authors.forename: Jiwu
authors.initials: J
authors.lastname: Wei
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy* / Q000821:virology; D000077192:Adenocarcinoma of Lung; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy* / Q000821:virology; D008459:Measles virus / Q000502:physiology*; D063306:Mitophagy / Q000502:physiology; D009336:Necrosis; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000502:physiology*; D014709:Vero Cells
chemical_list: D000255:Adenosine Triphosphate