Figure 1.

Role of CALCOCO1 during reticulophagy. During proteotoxic or nutrient stress, CALCOCO1 mediates the degradation of tubular ER through interaction with VAP proteins via its C-terminal FFAT-like motif. VAP-bound CALCOCO1 then recruits the autophagy machinery to the ER sites via LIR-LDS- and UIR-UDS-mediated interactions with Atg8-family proteins to initiate autophagosome biogenesis and capture of the degradable cargo. The cargo is subsequently sequestered into phagophores and then degraded when the mature autophagosomes fuse with lysosomes. CC, coiled coil; MSP, major sperm protein; PE, phosphatidylethanolamine; ZF, zinc finger.