APR3 modulates oxidative stress and mitochondrial function in ARPE-19 cells

Impairment of retinalpigment epithelial (RPE) cells is considered a keycontributor to thedevelopment of age-relatedmacular degeneration. Apoptosis-related protein 3 (APR3)was recently discovered after treatment with all-trans retinoic acid, a pivotalmolecule in RPE cells. However, the function of APR3 remains poorly understood. In the present study, we found that APR3 could interact with nuclear factor (erythroid-derived 2)-like 2, which is a regulator of phase II enzymes, and that knockdown of APR3 promoted nuclear factor (erythroid-derived 2)-like 2 nuclear translocation and activated expression of phase II enzymes, which was accompanied by improved redox status and mitochondrial activity. Overexpression of APR3 revealed its mitochondrial localization and induced a robust production of reactive oxygen species that was accompanied by impaired mitochondrial oxygen consumption, complex activity, and lower ATP content, resulting in significant changes in mitochondrial structure, which may contribute to cell apoptosis. High doses of all-trans retinoic acid treatment were found to significantly induce APR3 expression, increase reactive oxygen species levels, and decrease ATP content, which were abolished by knockdownofAPR3.These results indicate thatAPR3plays a vital role inregulating redox status andmitochondrial activity and thus suggest APR3 might be a potential novel target for study of treatment of age-related macular degeneration.