Cutting edge: ESCRT-mediated phagophore closure in mammals

Autophagy delivers cytoplasmic materials to lysosomes, supporting protein and organelle quality control as well as nutrient recycling to maintain cellular homeostasis. A defining feature of macroautophagy, the major form of autophagy, is the formation of double-membrane autophagosomes that encapsulate cargo either non-selectively or through selective recognition mechanisms. Completion of autophagosome biogenesis requires closure of the phagophore, a step that ensures full cargo sequestration and enables efficient degradation following lysosomal fusion. Recent studies have uncovered a critical role for the endosomal sorting complex required for transport (ESCRT) machinery in mediating phagophore closure, revealing that this event contributes to cellular functions beyond cargo degradation. In the present review, we summarize current advances in defining the molecular mechanisms and physiological significance of phagophore closure in mammals and highlight emerging concepts and future directions for the field.