Autophagy

Abstract Autophagy comprises several evolutionarily conserved mechanisms for uptake and transport of proteins and even cytoplasmic organelles to the lysosome for degradation. Although the importance of autophagy for cell homeostasis and survival has long been appreciated, our understanding of how autophagy is carried out at the molecular level has recently benefited from genetic studies that have revealed the functions of many of the participating proteins. The importance of autophagy for maintaining quality control on proteins and organelles is underscored by the fact that many diseases exhibit dysfunctional autophagic activities, for example neurodegenerative diseases. When cells undergoing stress leading to deoxyribonucleic acid damage, mitochondrial damage, and/or accumulation of damaged proteins are unable to induce a sufficient autophagic response, genetic instability ensues and such cells are prone to accumulate oncogenic mutations. Thus, autophagy is required for multiple roles in the prevention of human disease. Key Concepts Though a basal or constitutive level of autophagy is present in almost all cell types all the time for elimination of damaged proteins and even dysfunctional organelles, for example, mitochondria, autophagy can be strongly induced to compensate for nutritional imbalances or in response to stresses such as DNA damage. Autophagy is carried out by a set of more than 30 proteins encoded by the Autophagy‐Related genes ( ATGs ), the functions of which have been dissected using genetic and biochemical approaches. lncreasingly, it is becoming clear that proteins encoded by ATG genes carry out functions in cellular pathways independent of their roles in autophagy. Autophagy is a process in which a cup‐shaped, double‐membrane phagophore develops from a region of or near modified endoplasmic reticulum and closes, either unselectively in bulk or selectively, around sequestered cytoplasmic cargos, finally fusing with a lysosome to deliver the contents for degradation. Dysregulated autophagy contributes to many pathologic processes including cancer and neurodegenerative diseases.