The circadian protein CLOCK regulates cell metabolism via the mitochondrial carrier SLC25A10.

摘要: Physiological function and metabolic regulation are the most important outputs of circadian clock controls in mammals. Mitochondrial respiration ROS production show rhythmic activity. carriers, which responsible for mitochondrial substance transfer, vital metabolism. Clock (Circadian Locomotor Output Cycles Kaput) is first core gene identified mammalian animals. However, whether CLOCK protein can regulate functions via carriers unclear. Here, we showed that bind to carrier SLC25A10. For further analysis, established a Slc25a10-/--Hepa1-6 cell line using CRISPR/Cas9 gene-editing technology. cells disordered glucose homeostasis, increased oxidative stress levels, damaged electron transport chains. Next, an immunoprecipitation assay, found amino acids 43-84 169-210 SLC25A10 key sites respond binding. Finally, forced expression wild-type could compensate loss SLC25A10; decreased metabolism, severe chain were recovered. In addition, mutant Slc25a10 with changes two did not rescue effect. conclusion, new protein-protein interaction mechanism directly metabolism membrane transporter Our study might provide some insights into relationship between