ESCRT dysfunction compromises endoplasmic reticulum maturation and autophagosome biogenesis in Drosophila.

Autophagy targets cytoplasmic materials for degradation and influences cell health. Organelle contact and trafficking systems provide membranes for autophagosome formation, but how different membrane systems are selected for use during autophagy remains unclear. Here, we report a novel function of the endosomal sorting complex required for transport (ESCRT) in the regulation of endoplasmic reticulum (ER) coat protein complex II (COPII) vesicle formation that influences autophagy. The ESCRT functions in a pathway upstream of Vps13D to influence COPII vesicle transport, ER-Golgi intermediate compartment (ERGIC) assembly, and autophagosome formation. Atg9 functions downstream of the ESCRT to facilitate ERGIC and autophagosome formation. Interestingly, cells lacking either ESCRT or Vps13D functions exhibit dilated ER structures that are similar to cranio-lenticulo-sutural dysplasia patient cells with SEC23A mutations, which encodes a component of COPII vesicles. Our data reveal a novel ESCRT-dependent pathway that influences the ERGIC and autophagosome formation. [Display omitted] • The ESCRT and Vps13D function in a common autophagy pathway • The ESCRT influences ER maturation and COPII trafficking • Vps13D influences COPII trafficking • The ESCRT influences ERGIC and Vps13D availability for Atg9 induction of autophagy The removal of cytoplasmic materials by autophagy is important for cell and organism health. Wang et al. identify a relationship between the endosomal sorting complexes required for transport (ESCRT) and Vps13D in the regulation of endoplasmic reticulum (ER) coat protein complex II (COPII) vesicle formation that influences autophagy. [ABSTRACT FROM AUTHOR]