Regulation of Macroautophagy by Nutrients and Metabolites

The ability of cells to adapt to their microenvironment and to respond to changes in nutrient availability is essential for cell survival. Macroautophagy is one of the key cellular processes induced in response to environmental changes, nutrient starvation in particular. By sequestering and degrading cytoplasmic material (such as obsolete macromolecules, toxic protein aggregates, and defective organelles) basal macroautophagy maintains cellular homeostasis. The degradation of cytoplasmic material by macroautophagy is achieved within the lysosome, and the hydrolytic products (such as amino acids, sugars, fatty acids, and nucleotides) are recycled in the cytosol. When the supply of nutrients is limited, the induction of autophagy thus helps to maintain protein and ATP synthesis and allows cells to survive. In this review, we focus on the regulation of macroautophagy by nutrients and their metabolites. We describe how these molecules are sensed by the cell and how these sensing mechanisms are coupled to the regulation of autophagy. Finally, we discuss the importance of the nutrient diet and autophagy during aging and critical illness.