Bmal1 deletion alters mitochondrial microstructure and function in mouse cone photoreceptors

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 <i>Bmal1</i> in mitochondrial biology, we analyzed mitochondrial function and ultrastructure in 661W cells and mouse retinas lacking <i>Bmal1</i>. Loss of <i>Bmal1</i> impaired mitochondrial respiration, ATP production, and disrupted inner-membrane organization. Furthermore, we also identified <i>Mic60</i>, 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 <i>Bmal1</i>.