Antimycin A-Induced Mitochondrial Damage Causes Human RPE Cell Death despite Activation of Autophagy

Mitochondrial dysfunction has been implicated in a wide variety of degenerative diseases, including age-related macular degeneration. Damage to mitochondria and mitochondrial DNA accumulates with age in the postmitotic retinal pigment epithelium (RPE), which could lead to RPE cell death and trigger...

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Bibliographic Details
Published in:Oxidative medicine and cellular longevity 2019-01, Vol.2019 (2019), p.1-12
Main Authors: Kauppinen, Anu, Kaarniranta, Kai, Roehrich, Heidi, Hyttinen, Juha M. T., Korhonen, Eveliina, Hytti, Maria, Ferrington, Deborah A.
Format: Article
Language:English
Subjects:
Age
Apoptosis
Autophagy
Biochemistry
Biotechnology industry
Cell cycle
Cell death
Cytochrome b
Cytotoxicity
Deoxyribonucleic acid
DNA
DNA damage
Electron transport
Investigations
Macular degeneration
Mitochondria
Mitochondrial DNA
Mutation
Oxidative stress
Production increases
Protein expression
Proteins
Scientific equipment and supplies industry
Toxicology
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Summary:Mitochondrial dysfunction has been implicated in a wide variety of degenerative diseases, including age-related macular degeneration. Damage to mitochondria and mitochondrial DNA accumulates with age in the postmitotic retinal pigment epithelium (RPE), which could lead to RPE cell death and trigger disease. One possible mechanism for cells to avoid cell death is mitophagy, the targeted clearance of damaged mitochondria by autophagy. Here, we induced mitochondrial damage in human RPE cells (ARPE-19 and hRPE), using antimycin A, an inhibitor of complex III of the electron transport chain, and investigated cellular viability, mitochondrial structure and function, and autophagy activity. We observed that antimycin A evoked dose-dependent cell death, a rapid loss in mitochondrial membrane potential, and a collapse of oxidative phosphorylation. Mitochondria appeared swollen and there was clear damage to their cristae structure. At the same time, cells were undergoing active autophagy and were sensitive to autophagy inhibition by bafilomycin A1 or chloroquine. These results indicate that mitochondrial dysfunction can cause significant RPE damage and that autophagy is an important survival mechanism for cells suffering from mitochondrial damage.
ISSN:1942-0900
1942-0994
DOI:10.1155/2019/1583656