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Tumour Biol. 2017 Oct;39(10):1010428317733985. doi: 10.1177/1010428317733985.

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

Author information

1
1 Immunotherapy Convergence Research Group, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Republic of Korea.
2
2 Department of Biomolecular Science, University of Science & Technology (UST), Daejeon, Republic of Korea.
3
3 Department of Biochemistry, College of Natural Science, Chungbuk National University, Cheongju, Republic of Korea.
4
4 World Class Institute, Korea Research Institute of Bioscience & Biotechnology, Cheongju, Republic of Korea.
5
5 Department of Infection Biology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.

Abstract

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.

KEYWORDS:

Opa-interacting protein 5; cell death; docetaxel; mitochondrial depolarization; mitophagy

PMID:
29034772
DOI:
10.1177/1010428317733985
[Indexed for MEDLINE]

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