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.