Diurnal Rhythms Spatially and Temporally Organize Autophagy

Abstract

Summary: Circadian rhythms are a hallmark of physiology, but how such daily rhythms organize cellular catabolism is poorly understood. Here, we used proteomics to map daily oscillations in autophagic flux in mouse liver and related these rhythms to proteasome activity. We also explored how systemic inflammation affects the temporal structure of autophagy. Our data identified a globally harmonized rhythm for basal macroautophagy, chaperone-mediated autophagy, and proteasomal activity, which concentrates liver proteolysis during the daytime. Basal autophagy rhythms could be resolved into two antiphase clusters that were distinguished by the subcellular location of targeted proteins. Inflammation induced by lipopolysaccharide reprogrammed autophagic flux away from a temporal pattern that favors cytosolic targets and toward the turnover of mitochondrial targets. Our data detail how daily biological rhythms connect the temporal, spatial, and metabolic aspects of protein catabolism. : How circadian rhythms contribute to cellular quality control is poorly understood. Ryzhikov et al. mapped proteome-wide biological rhythms in liver autophagy and identified synchronous daily oscillations in autophagic and proteasomal activity. Diurnal rhythms play a role in autophagy substrate selection based on subcellular location and inflammation status. Keywords: macroautophagy, autophagy, chaperone-mediated autophagy, proteasome, circadian rhythm, lipopolysaccharide, endotoxin, inflammation, clock