Autophagy - how to control your intracellular diet

The most recent Nobel Prize in Physiology together with the prospect of new drugs for the benefit of patients with infectious, malignant, or ageing‐associated diseases has moved research on autophagy into the limelight – a place well deserved, also in dermatology. Autophagy, literally ‘self‐eating’, is a degradation process for intracellular proteins, lipids, carbohydrates and subcellular organelles. The delineation of its molecular mechanisms, governed by specific Autophagy‐related (Atg) genes,1 was awarded with the Nobel Prize to Professor Yoshinori Ohsumi in 2016.2 This line of research has yielded many potential targets for drug development, and several already existing drugs turn out to affect the rate and efficiency of autophagy.3 Yet, the full potential of autophagy remains to be defined and translated into medical practice. In a simplified portrayal, autophagy achieves, within a cell, what apoptosis and phagocytosis achieve within the tissue, that is, the removal of superfluous, damaged or dangerous components (Fig. 1). Ultimately, both pathways converge in lysosomal degradation of self‐material. While apoptosis starts with limited proteolysis and cell fragmentation to yield apoptotic bodies that are suitable for ingestion by other cells, autophagy begins with the formation of double‐membraned vesicles (autophagosomes) inside cells. The vesicles enclose parts of the cytoplasm as well as organelles and, subsequently, like phagosomes in phagocytes, fuse with lysosomes to expose their cargo to an array of hydrolytic enzymes.1 The breakdown products of the cargo are subsequently released into the cytoplasm and re‐enter cellular metabolism (Fig. 1).