Confine to create: ER-endosome contacts foster autophagy initiation

Autophagy is a conserved cellular process in which eukaryotic cells degrade and recycle intracellular material via a dedicated trafficking toward lysosomes. Under starvation, autophagy is initiated by the formation of a double-membrane organelle called the autophagosome, which originates from the closure and maturation of a transient membrane structure known as the phagophore. The precise membrane source of the phagophore and the mechanisms underlying its biogenesis remain incompletely understood. In our recent study by Da Graça et al., we show that starvation dynamically mobilizes endoplasmic reticulum (ER)-endosome contacts to initiate phagophore formation. Our data reveal that the ER–endosome interface facilitates local calcium release and phase transition, driving the mobilization of nanovesicles, which then fuse via a Rab3-dependent mechanism to assemble the phagophore. These findings highlight a central role for ER-endosome communication in the cellular response to nutritional stress and in the regulation of autophagy.