Diurnal rhythms of autophagy: implications for cell biology and human disease

Autophagy is a key mechanism for cell survival under conditions of nutrient limitation. On the organismal level, autophagy is essential for survival of lower eukaryotes during extended periods of starvation, and it is induced in mammals during short-term starvation. As a consequence of the induction of autophagy during short periods of fasting, animals experience diurnal rhythms of autophagy in concert with their circadian cycle. Autophagy has also been identified as a component of the metabolic cycle of yeast, an ultradian rhythm that bears many similarities to the circadian rhythm of plants, flies and mammals. The circadian clock, which is present in almost all mammalian cell types studied to date, temporally regulates expression of multiple genes, gating cell processes such as nutrient uptake, glycolysis, and proliferation, to particular times of day. Whether the circadian clock directly regulates autophagy in mammalian cells, or whether autophagy may play a role in the cycling of mammalian cell clocks is not yet clear. Nevertheless, the relationship between circadian cycles and autophagy is an intriguing area for future study and has implications for multiple human diseases, including aging, neurodegeneration and cancer.