Autophagy initiation

Autophagy is a remarkable pathway for cellular self-digestion and renewal. Autophagy entails the engulfment of bulk cytosol, molecular condensates, damaged or unneeded mitochondria (“mitophagy”), and protein aggegrates within a double membrane vesicle, the phagophore. Whether or not autophagy initiation occurs can be a make-or-break decision that permits a cell to survive or not. Our laboratory uses cryo-EM, x-ray crystallography, HDX-MS, and biophysical membrane reconstitution to determine the molecular mechanisms whereby autophagy in general and mitophagy in particular are initiated. Insights from recent reconstitutions and structural studies of human mitophagy initiation will be discussed.