Autophagy: clocking in for the night shift

Abstract

Daily rhythms of biological activity, such as cycles of sleep–wake and feeding–fasting, are coupled to cell‐autonomous circadian clocks to synchronize organismal food intake with cellular bioenergetics. Food intake during wake stimulates biosynthesis followed by rest periods of autophagy, which degrades damaged macromolecules and recycles them as nutrients to enhance fitness. In this issue of The EMBO Journal, Pastore et al discovered that regulators of autophagy, TFEB and TFE3, are activated during the rest phase and ultimately drive the expression of Rev‐erbα, a component of the core circadian molecular clock, coupling autophagy and the clock.

Figure 1. TFEB/TFE3 connect the nutrient sensitive clock to the circadian molecular clock

(A) TFEB/TFE3‐mediated regulation of autophagy and clock‐controlled genes, through Rev‐erbα, is driven by nutrient intake and mTORC1, and not the molecular clock. (B) The circadian molecular clock and the nutrient‐sensitive clock, antiphase mTORC1 activation and autophagy, collaborate to drive diurnal metabolic oscillations.