Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, Texas.
Interdisciplinary Toxicology Program, Texas A&M University, College Station, Texas.
J Biol Rhythms. 2018 Apr;33(2):151-165. doi: 10.1177/0748730418762152.
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.
脊椎动物视网膜中的能量消耗和代谢受昼夜节律控制，正如我们之前报道的，整个视网膜 ATP 含量和各种与代谢相关的信号分子都呈现出日常或昼夜节律。产生 ATP 的主要细胞器——线粒体的裂变和融合过程的变化在很大程度上依赖于光暴露，但光感受器和视网膜神经元中线粒体动力学是否受昼夜节律控制尚不清楚。在此，我们研究了昼夜节律振荡器在调节鸡视网膜和哺乳动物光感受器中线粒体动力学、线粒体自噬和氧化还原状态中的可能作用。在连续几天适应 12:12 小时明暗（LD）循环后，在持续黑暗（DD）中自由运行，在 6 个不同的时间（ZT）或昼夜时间（CT）点，分别在 LD 或 DD 下收集鸡胚胎视网膜和锥体细胞衍生的 661W 细胞。线粒体动力相关蛋白 1（DRP1）、融合蛋白 2（MFN2）和 PTEN 诱导假定激酶 1（PINK1）的蛋白表达呈现出日节律，但在鸡视网膜和培养的 661W 细胞中，只有 DRP1 受昼夜节律控制。此外，培养的鸡视网膜细胞对急性氧化应激的反应与 661W 细胞不同。使用 pMitoTimer 作为线粒体氧化还原指示剂，我们发现线粒体氧化还原状态受光暴露的影响大于受昼夜节律振荡器的调节。因此，本研究表明，周期性光照的影响可能大于光感受器中复杂线粒体动力学的昼夜节律调节。
