The spatiotemporal control of ER membrane fragmentation during reticulophagy

ABSTRACTReticulophagy is an evolutionarily conserved mechanism essential to maintain the endoplasmic reticulum (ER) homeostasis. A series of studies identified a panel of reticulophagy receptors. However, it remains unclear how these receptors sense upstream signals for spatiotemporal control of reticulophagy and how ER is fragmented into small pieces for sequestration into phagophores. Recently, we and others showed that the oligomerization of RETREG1/FAM134B (reticulophagy regulator 1), an reticulophagy receptor, triggers the scission of ER membrane to facilitate reticulophagy. Furthermore, we demonstrated that upstream signals are transduced by sequential phosphorylation and acetylation of RETREG1, which stimulate its oligomerization, ER fragmentation and reticulophagy. Our work provides further mechanistic insights into how reticulophagy receptor conveys cellular signals to fine-tune of ER homeostasis.Abbreviations: ER, endoplasmic reticulum; MAP1LC3, microtubule-associated protein light chain 3; RETREG1, reticulophagy regulator 1; RHD, reticulon-homology domainKEYWORDS: acetylationmembrane fragmentationphosphorylationreticulophagyRETREG1 Disclosure statementNo potential conflict of interest was reported by the authors.Additional informationFundingThis study is supported by The National Natural Science Foundation under Grant 32025012, 92254307, 31970695, 31771525 to Q.S, and by Ministry of Science and Technology of the People’s Republic of China under Grant 2021YFC2700901 to Q. S.