Hva22, a REEP family protein in fission yeast, promotes reticulophagy in collaboration with a receptor protein

The endoplasmic reticulum (ER) undergoes selective autophagy called reticulophagy or ER-phagy. Multiple reticulon- and receptor expression enhancing protein (REEP)-like ER-shaping proteins, including budding yeast Atg40, serve as reticulophagy receptors that stabilize the phagophore on the ER by interacting with phagophore-conjugated Atg8. Additionally, they facilitate phagophore engulfment of the ER by remodeling ER morphology. We reveal that Hva22, a REEP family protein in fission yeast, promotes reticulophagy without Atg8-binding capacity. The role of Hva22 in reticulophagy can be replaced by expressing Atg40 independently of its Atg8-binding ability. Conversely, adding an Atg8-binding sequence to Hva22 enables it to substitute for Atg40 in budding yeast. Thus, the phagophore-stabilizing and ER-shaping activities, both of which Atg40 solely contains, are divided between two separate factors, receptors and Hva22, respectively, in fission yeast.

Automated summary

The endoplasmic reticulum (ER) undergoes selective autophagy called reticulophagy or ER-phagy. Reticulon- and receptor expression enhancing protein (REEP)-like ER-shaping proteins, such as budding yeast Atg40, act as reticulophagy receptors to stabilize the phagophore on the ER by interacting with phagophore-conjugated Atg8. Hva22, a REEP family protein in fission yeast, promotes reticulophagy without Atg8-binding capacity and its role can be replaced by expressing Atg40 independently of its Atg8-binding ability.