Opa-interacting protein 5 modulates docetaxel-induced cell death via regulation of mitophagy in gastric cancer

• Published in: Tumor biology 2017-10, Vol.39 (10), p.1010428317733985-1010428317733985
• Main Authors: Kim, Tae Woo, Lee, Seon-Jin, Park, Young-Jun, Park, Sang Yoon, Oh, Byung Moo, Park, Yun Sun, Kim, Bo-Yeon, Lee, Young-Ha, Cho, Hee Jun, Yoon, Suk Ran, Choe, Yong-Kyung, Lee, Hee Gu
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; ATP; Autophagy; Breast cancer; Cancer therapies; Cell culture; Cell death; Cell Death - drug effects; Cell Line, Tumor; Cell survival; Cell Survival - drug effects; Cell Survival - physiology; Chemotherapy; Chromosomal Proteins, Non-Histone - metabolism; Depolarization; Endoplasmic reticulum; Gastric cancer; GTP Phosphohydrolases - metabolism; Homology; Humans; Kinases; Medical research; Melanoma; Membrane proteins; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial Degradation - drug effects; Mitochondrial Degradation - physiology; Mitochondrial DNA; Mitochondrial Proteins - metabolism; Mitophagy; Motility; Neisseria gonorrhoeae; Neisseria gonorrhoeae - metabolism; Opacity; Outer membrane proteins; Phosphoric Monoester Hydrolases - metabolism; Proteins; PTEN protein; Reactive oxygen species; Reactive Oxygen Species - metabolism; Ribonucleic acid; RNA; RNA, Small Interfering - metabolism; siRNA; Stomach Neoplasms - metabolism; Taxoids - pharmacology; Tensin; Tensins - metabolism
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1177/1010428317733985

Damage to mitochondria induces mitophagy, a cellular process that is gaining interest for its therapeutic relevance to a variety of human diseases. However, the mechanism underlying mitochondrial depolarization and clearance in mitophagy remains poorly understood. We previously reported that mitochondria-induced cell death was caused by knockdown of Neisseria gonorrhoeae opacity-associated-interacting protein 5 in gastric cancer. In this study, we show that Neisseria gonorrhoeae opacity-associated-interacting protein 5 loss and gain of function modulates mitophagy induced by treatment with docetaxel, a chemotherapy drug for gastric cancer. The activation of mitophagy by Neisseria gonorrhoeae opacity-associated-interacting protein 5 overexpression promoted cell survival, preventing docetaxel-induced mitochondrial clearance. Conversely, short interfering RNA–mediated knockdown of Neisseria gonorrhoeae opacity-associated-interacting protein 5 accelerated docetaxel-induced apoptosis while increasing mitochondrial depolarization, reactive oxygen species, and endoplasmic reticulum stress and decreasing adenosine triphosphate production. We also found that the mitochondrial outer membrane proteins mitofusin 2 and phosphatase and tensin homolog–induced putative kinase 1 colocalized with Neisseria gonorrhoeae opacity-associated-interacting protein 5 in mitochondria and that mitofusin 2 knockdown altered Neisseria gonorrhoeae opacity-associated-interacting protein 5 expression. These findings indicate that Neisseria gonorrhoeae opacity-associated-interacting protein 5 modulates docetaxel-induced mitophagic cell death and therefore suggest that this protein comprises a potential therapeutic target for gastric cancer treatment.