MITF acts as an anti-oxidant transcription factor to regulate mitochondrial biogenesis and redox signaling in retinal pigment epithelial cells

There is increasing evidence that the mechanisms protecting the retinal pigment epithelium (RPE) against oxidative stress are important for preventing retinal degenerative diseases Little, however, is known about these mechanisms. Here we show that MITF, a transcription factor responsible for RPE development and function, regulates redox signaling by acting through PGCl alpha, a master regulator of mitochondrial biogenesis. Mitf deficiency in mice leads to significantly higher levels of reactive oxygen species (ROS) in both RPE and retina, suggesting that Mitf dysfunction might lead to oxidative damage in the RPE and, by extension, in the retina. Furthermore, overexpression of MITF m the human RPE cell line ARPE-19 indicates that MITF up-regulates antioxidant gene expression and mitochondrial biogenesis by regulating PGCl alpha and protects cells against oxidative stress. Our findings provide new insights into understanding the redox function of MITF in RPE cells and its potential contribution to prevention of RPE-associated retinal degenerations.