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

Maria Hytti, Eveliina Korhonen, Juha M.T. Hyttinen, Heidi Roehrich, Kai Kaarniranta, Deborah A Ferrington, Anu Kauppinen

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number1583656
JournalOxidative medicine and cellular longevity
Volume2019
DOIs
StatePublished - Jan 1 2019

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Antimycin A
Retinal Pigments
Retinal Pigment Epithelium
Autophagy
Cell death
Mitochondria
Cell Death
Chemical activation
Mitochondrial Degradation
Electron Transport Complex III
Chloroquine
Mitochondrial DNA
Mitochondrial Membrane Potential
Oxidative Phosphorylation
Macular Degeneration
Membranes
Cell Survival

PubMed: MeSH publication types

  • Journal Article

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Antimycin A-Induced Mitochondrial Damage Causes Human RPE Cell Death despite Activation of Autophagy. / Hytti, Maria; Korhonen, Eveliina; Hyttinen, Juha M.T.; Roehrich, Heidi; Kaarniranta, Kai; Ferrington, Deborah A; Kauppinen, Anu.

In: Oxidative medicine and cellular longevity, Vol. 2019, 1583656, 01.01.2019.

Research output: Contribution to journalArticle

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AU - Kaarniranta, Kai

AU - Ferrington, Deborah A

AU - Kauppinen, Anu

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