Regulation of autophagy-transcriptional, posttranscriptional, translational, and posttranslational mechanisms

Autophagy is a cellular catabolic pathway. During autophagy, cargo targeted for degradation is engulfed in double-membrane vesicles and delivered to the lysosome, where hydrolytic enzymes produce recycled metabolites. Autophagy is a necessary component in cellular stress response and is therefore regulated at several levels. This chapter reviews the modulation of autophagy at the posttranslational, transcriptional, and epigenetic regulatory levels. We discuss the role of phosphorylation by the nutrient-sensitive kinases mTOR and AMPK in the induction of autophagy and the role of ubiquitin-mediated degradation in restraining autophagy. We outline the role of the MiT/TFE family of proteins in regulating autophagy-lysosomal genes and how the regulation of MiT/TFE protein localization and stability controls lysosomal activity. We also describe the role of transcription factors, such as the FOXO, ZKSCAN3, and FOXO, in activating or repressing autophagy. Lastly, we describe how epigenetic remodeling through histone modification and regulation of protein translation contributes to regulation of autophagy activity. Altogether, we aim to show how multiple systems interact to ensure controlled activation of autophagy in response to stress and how autophagy regulation is a critical component in the orchestration of metabolism.