Circadian Regulation of Mitochondrial Dynamics in Retinal Photoreceptors

Energy expenditure and metabolism in the vertebrate retina are under circadian control, as we previously reported that the overall retinal ATP content and various signaling molecules related to metabolism display daily or circadian rhythms. Changes in the fission and fusion process of mitochondria, the major organelles producing ATP, in retinal photoreceptors are largely dependent on light exposure, but whether mitochondrial dynamics in photoreceptors and retinal neurons are under circadian control is not clear. Herein, we investigated the possible roles of circadian oscillators in regulating mitochondrial dynamics, mitophagy, and redox states in the chicken retina and mammalian photoreceptors. After entrainment to 12:12-h light-dark (LD) cycles for several days followed by free-running in constant darkness (DD), chicken embryonic retinas and cone-derived 661W cells were collected in either LD or DD at 6 different zeitgeber time (ZT) or circadian time (CT) points. The protein expression of mitochondrial dynamin-related protein 1 (DRP1), mitofusin 2 (MFN2), and PTEN-induced putative kinase 1 (PINK1) displayed daily rhythms, but only DRP1 was under circadian control in the chicken retinas and cultured 661W cells. In addition, cultured chicken retinal cells responded to acute oxidative stress differently from 661W cells. Using pMitoTimer as a mitochondrial redox indicator, we found that the mitochondrial redox states were more affected by light exposure than regulated by circadian oscillators. Thus, this study demonstrates that the influence of cyclic lights might outweigh the circadian regulation of complex mitochondrial dynamics in light-sensing retinal cells.