Bmal1 Deletion Alters Mitochondrial Microstructure and Function in Mouse Cone Photoreceptors

Description

The mammalian retina contains an autonomous circadian system that regulates several functions. Previous studies have shown that removing the clock gene Bmal1 from the mouse retina affects retinal circuitry, cone photoreceptor spectral identity, and cone viability during aging. However, the cellular and molecular underpinnings of these effects remain unclear. Among retinal cells, cone photoreceptors have the highest demand for energy. They are also continuously exposed to high levels of oxidative stress, which can damage their mitochondria and compromise cell viability. In the present study, we investigated the effect of Bmal1 removal on mitochondrial function and their ultrastructure in 661W cells, a cone-like photoreceptor cell line and in the retinas of mice lacking retinal Bmal1 (rBKO). Our results show that the removal of Bmal1 from 661W cells (BKO) reduced mitochondrial respiration and ATP production. Removal of Bmal1 from the 661W cells or the mouse retina also disrupts mitochondrial structure and inner-membrane organization. Furthermore, we found that BMAL1 directly regulates the circadian expression of Mitofilin, a key mitochondrial inner-membrane protein that maintains cristae structure. These datasets contain the original raw images and values used for our analysis in each figure of the research manuscript.

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As indicated in the manuscript methods part, electron microscope JEOL 1200EX electron microscope, Seahorse Extracellular Flux XFp analyzers (Agilent) for measurement of oxygen consumption rate, CFX96 Touch Real-Time PCR Detection System (Bio-Rad) for gene detection and these manufacture software had been used to measure and analyze observed data.

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