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

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 mitocho...

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Main Authors: Tae Woo Kim, Seon-Jin Lee, Young-Jun Park, Sang Yoon Park, Byung Moo Oh, Yun Sun Park, Bo-Yeon Kim, Young-Ha Lee, Hee Jun Cho, Suk Ran Yoon, Yong-Kyung Choe, Hee Gu Lee
Format: Article
Language:English
Published: SAGE Publishing 2017-10-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428317733985
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author Tae Woo Kim
Seon-Jin Lee
Young-Jun Park
Sang Yoon Park
Byung Moo Oh
Yun Sun Park
Bo-Yeon Kim
Young-Ha Lee
Hee Jun Cho
Suk Ran Yoon
Yong-Kyung Choe
Hee Gu Lee
author_facet Tae Woo Kim
Seon-Jin Lee
Young-Jun Park
Sang Yoon Park
Byung Moo Oh
Yun Sun Park
Bo-Yeon Kim
Young-Ha Lee
Hee Jun Cho
Suk Ran Yoon
Yong-Kyung Choe
Hee Gu Lee
author_sort Tae Woo Kim
collection DOAJ
description 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.
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spelling doaj-art-1b05d75414ae4bb996b725c1795deda72025-08-20T03:15:16ZengSAGE PublishingTumor Biology1423-03802017-10-013910.1177/1010428317733985Opa-interacting protein 5 modulates docetaxel-induced cell death via regulation of mitophagy in gastric cancerTae Woo Kim0Seon-Jin Lee1Young-Jun Park2Sang Yoon Park3Byung Moo Oh4Yun Sun Park5Bo-Yeon Kim6Young-Ha Lee7Hee Jun Cho8Suk Ran Yoon9Yong-Kyung Choe10Hee Gu Lee11Department of Biomolecular Science, University of Science & Technology (UST), Daejeon, Republic of KoreaDepartment of Biomolecular Science, University of Science & Technology (UST), Daejeon, Republic of KoreaDepartment of Biomolecular Science, University of Science & Technology (UST), Daejeon, Republic of KoreaDepartment of Biochemistry, College of Natural Science, Chungbuk National University, Cheongju, Republic of KoreaDepartment of Biomolecular Science, University of Science & Technology (UST), Daejeon, Republic of KoreaImmunotherapy Convergence Research Group, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Republic of KoreaWorld Class Institute, Korea Research Institute of Bioscience & Biotechnology, Cheongju, Republic of KoreaDepartment of Infection Biology, School of Medicine, Chungnam National University, Daejeon, Republic of KoreaImmunotherapy Convergence Research Group, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Republic of KoreaImmunotherapy Convergence Research Group, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Republic of KoreaImmunotherapy Convergence Research Group, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Republic of KoreaDepartment of Biomolecular Science, University of Science & Technology (UST), Daejeon, Republic of KoreaDamage 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.https://doi.org/10.1177/1010428317733985
spellingShingle Tae Woo Kim
Seon-Jin Lee
Young-Jun Park
Sang Yoon Park
Byung Moo Oh
Yun Sun Park
Bo-Yeon Kim
Young-Ha Lee
Hee Jun Cho
Suk Ran Yoon
Yong-Kyung Choe
Hee Gu Lee
Opa-interacting protein 5 modulates docetaxel-induced cell death via regulation of mitophagy in gastric cancer
Tumor Biology
title Opa-interacting protein 5 modulates docetaxel-induced cell death via regulation of mitophagy in gastric cancer
title_full Opa-interacting protein 5 modulates docetaxel-induced cell death via regulation of mitophagy in gastric cancer
title_fullStr Opa-interacting protein 5 modulates docetaxel-induced cell death via regulation of mitophagy in gastric cancer
title_full_unstemmed Opa-interacting protein 5 modulates docetaxel-induced cell death via regulation of mitophagy in gastric cancer
title_short Opa-interacting protein 5 modulates docetaxel-induced cell death via regulation of mitophagy in gastric cancer
title_sort opa interacting protein 5 modulates docetaxel induced cell death via regulation of mitophagy in gastric cancer
url https://doi.org/10.1177/1010428317733985
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