Abstract
The mammalian retina contains an autonomous circadian system that regulates ocular physiology. The deletion of the core clock gene Bmal1 in the mouse retina disrupts retinal circuitry, alters cone spectral identity, and reduces cone viability. Cone photoreceptors have the highest energy demand among retinal neurons and are continuously exposed to high levels of oxidative stress, making them susceptible to mitochondrial dysfunction. To investigate the role of Bmal1 in mitochondrial biology, we analyzed mitochondrial function and ultrastructure in 661W cells and mouse retinas lacking Bmal1. Loss of Bmal1 impaired mitochondrial respiration, ATP production, and disrupted inner-membrane organization. Furthermore, we also identified Mic60, a key regulator of cristae structure as a direct transcriptional target of BMAL1. These findings highlight a critical role for Bmal1 in mitochondrial integrity and suggest a potential mechanism to explain the reduced cone viability observed in mice lacking Bmal1.
Keywords:
biochemistry; cell biology; specialized functions of cells.