title: Retinal pigment epithelial cells undergoing mitotic catastrophe are vulnerable to autophagy inhibition.
abstract: The increased mitochondrial DNA damage leads to altered functional capacities of retinal pigment epithelial (RPE) cells. A previous study showed the increased autophagy in RPE cells caused by low concentrations of rotenone, a selective inhibitor of mitochondrial complex I. However, the mechanism by which autophagy regulates RPE cell death is still unclear. In the present study, we examined the mechanism underlying the regulation of RPE cell death through the inhibition of mitochondrial complex I. We report herein that rotenone induced mitotic catastrophe (MC) in RPE cells. We further observed an increased level of autophagy in the RPE cells undergoing MC (RPE-MC cells). Importantly, autophagy inhibition induced nonapoptotic cell death in RPE-MC cells. These findings indicate that autophagy has a pivotal role in the survival of RPE-MC cells. We next observed PINK1 accumulation in the mitochondrial membrane and parkin translocation into the mitochondria from the cytosol in the rotenone-treated RPE-MC cells, which indicates that increased mitophagy accompanies MC in ARPE-19 cells. Noticeably, the mitophagy also contributed to the cytoprotection of RPE-MC cells. Although there might be a significant gap in the roles of autophagy and mitophagy in the RPE cells in vivo, our in vitro study suggests that autophagy and mitophagy presumably prevent the RPE-MC cells from plunging into cell death, resulting in the prevention of RPE cell loss.
authors: 1] Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan, South Korea [2] Department of Rheumatology, Dong-A University College of Medicine, Busan, South Korea.
authors: S Y
authors: SY
authors: Lee
authors: 1] Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan, South Korea [2] Bong Seng Memorial Hospital, Busan, South Korea.
authors: J S
authors: JS
authors: Oh
authors: Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan, South Korea.
authors: J H
authors: JH
authors: Rho
authors: Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan, South Korea.
authors: N Y
authors: NY
authors: Jeong
authors: Department of Ophthalmology, Dong-A University College of Medicine, Busan, South Korea.
authors: Y H
authors: YH
authors: Kwon
authors: Department of Ophthalmology, Dong-A University College of Medicine, Busan, South Korea.
authors: W J
authors: WJ
authors: Jeong
authors: Department of Ophthalmology, Dong-A University College of Medicine, Busan, South Korea.
authors: W Y
authors: WY
authors: Ryu
authors: Department of Ophthalmology, Dong-A University College of Medicine, Busan, South Korea.
authors: H B
authors: HB
authors: Ahn
authors: Department of Ophthalmology, Dong-A University College of Medicine, Busan, South Korea.
authors: W C
authors: WC
authors: Park
authors: Department of Ophthalmology, Dong-A University College of Medicine, Busan, South Korea.
authors: S H
authors: SH
authors: Rho
authors: Department of Biomedical Science, Jungwon University, Goesan, South Korea.
authors: Y G
authors: YG
authors: Yoon
authors: Department of Medical Genetics, Ajou University School of Medicine, Suwon, Republic of Korea.
authors: S-Y
authors: SY
authors: Jeong
authors: Department of Biochemistry and Research Institute of Oriental Medicine, Dongeui University College of Oriental Medicine, Busan, South Korea.
authors: Y H
authors: YH
authors: Choi
authors: Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan, South Korea.
authors: H Y
authors: HY
authors: Kim
authors: Department of Anatomy and Cell Biology, Dong-A University College of Medicine and Mitochondria Hub Regulation Center, Busan, South Korea.
authors: Y H
authors: YH
authors: Yoo
mesh_terms: D001343:Autophagy / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D042967:Electron Transport Complex I / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D042967:Electron Transport Complex I