Fission yeast ortholog of REEP1-4 promotes autophagosomal enclosure of ER-phagy/nucleophagy cargos

Selective macroautophagy of the endoplasmic reticulum (ER) and the nucleus, referred to as ER-phagy and nucleophagy, respectively, are processes whose mechanisms remain incompletely understood. Through an imaging-based screen, we find that fission yeast Yep1, the ortholog of human REEP1-4, is essential for ER-phagy and nucleophagy. Yep1 is required for the autophagosomal enclosure of cargos during ER-phagy and nucleophagy. In its absence, membrane structures derived from the nucleus and cortical ER accumulate in the cytoplasm. Its ER-phagy role depends on its abilities to self-interact and shape membranes, and requires its C-terminal amphipathic helices. In addition, we show that human REEP1-4 and budding yeast Atg40 can substitute for the ER-phagy function of Yep1, and Atg40 is a divergent homolog of Yep1 and REEP1-4. Our study unveils an unexpected mechanism governing the autophagosomal enclosure of ER-phagy/nucleophagy cargos, and sheds new light on the functions and evolution of REEP family proteins.