Abstract
Circadian rhythms are physical, behavioral and environmental cycles that respond primarily to light and dark, with a period of time of approximately 24 h. The most essential physiological functions of mammals are manifested in circadian rhythm patterns, including the sleep-wake cycle and nutrient and energy metabolism. Autophagy is a conserved biological process contributing to nutrient and cellular homeostasis. The factors affecting autophagy are numerous, such as diet, drugs, and aging. Recent studies have indicated that autophagy is activated rhythmically in a clock-dependent manner whether the organism is healthy or has certain diseases. In addition, autophagy can affect circadian rhythm by degrading circadian proteins. This review discusses the interaction and mechanisms between autophagy and circadian rhythm. Moreover, we introduce the molecules influencing both autophagy and circadian rhythm. We then discuss the drugs affecting the circadian rhythm of autophagy. Finally, we present the role of rhythmic autophagy in nutrient and energy metabolism and its significance in physiology and metabolic disease.
Highlights
Autophagy is an intracellular degradative procedure that targets cytosolic components to lysosomes for degradation to maintain cellular homeostasis and provide substrates for energy generation (Farias et al, 2019; Santin-Marquez et al, 2019; Yan et al, 2019)
CCAAT/enhancer binding protein β (C/EBPβ) is emerging as a significant factor involved in rhythmic autophagy gene expression, such as Unc-51-like autophagy activating kinase (ULK1), microtubule-associated protein 1A/1B-light chain 3B (LC3B), BCL2/adenovirus E1B interacting protein 3 (BNIP3) and GABA (A) receptor-associated protein like 1 (GABARAPL1), which are expressed in an oscillating manner and are mediated by circadian and nutritional signals (Ma and Lin, 2012)
Recent studies have found that TFEB and TFE3 are activated in a circadian manner and promote the expression of Rev-erbα (Nr1d1), a transcription inhibitor component of the main clock machinery that controls autophagy-related gene expression, such as BECLIN-1, BNIP3, ATG5, ATG7, and ULK1, their depletion damages Rev-erbα expression and oscillation (Pastore et al, 2019)
Summary
Autophagy is an intracellular degradative procedure that targets cytosolic components to lysosomes for degradation to maintain cellular homeostasis and provide substrates for energy generation (Farias et al, 2019; Santin-Marquez et al, 2019; Yan et al, 2019). BMAL1:CLOCK complex can activate the transcription of genes, participating in regulating many cell processes, such as ATG14, BNIP3, BECLIN-1.
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