Reticulon-dependent ER-phagy mediates adaptation to heat stress in C. elegans.

The selective degradation of endoplasmic reticulum (ER) by autophagy, named ER-phagy, promotes the recovery of ER homeostasis after stress. Depending on the ER stress, different types of ER-phagy involve various selective autophagy receptors. In this study, we report a macroER-phagy induced by the fragmentation of tubular ER in response to acute heat stress. We identified a novel ER-phagy receptor encoded by the reticulon long isoform RET-1d. RET-1d is mainly expressed in the nervous system and the epidermis and colocalizes with the ubiquitin-like autophagy protein LGG-1/GABARAP during heat-stress-induced autophagy. Two LC3-interacting region (LIR) motifs in the long intrinsically disordered region of RET-1d mediate its interaction with the LGG-1 protein. The specific depletion of the RET-1d isoform or the mutations of the LIRs resulted in a defective ER-phagy and a decrease in the capacity of animals to adapt to heat stress. Our data revealed a RET-1d- and LGG-1-dependent ER-phagy mechanism that takes place in neurons and epidermis and participates in the adaptation of C. elegans to heat stress.