2026-04-29T04:09:11Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/150262024-11-29T20:11:17Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Di Lorenzo, Giorgia author Iavarone, Francescopaolo author Maddaluno, Marianna author Plata-Gómez, Ana Belén author Aureli, Simone author Quezada Meza, Camila Paz author Cinque, Laura author Palma, Alessandro author Reggio, Alessio author Cirillo, Carmine author Sacco, Francesca author Stolz, Alexandra author Napolitano, Gennaro author Marin, Oriano author Pinna, Lorenzo A author Ruzzene, Maria author Limongelli, Vittorio author Efeyan, Alejo author Grumati, Paolo author Settembre, Carmine author Pinna, Lorenzo A. author 2022-09-02 Selective degradation of the endoplasmic reticulum (ER) via autophagy (ER-phagy) is initiated by ER-phagy receptors, which facilitate the incorporation of ER fragments into autophagosomes. FAM134 reticulon family proteins (FAM134A, FAM134B, and FAM134C) are ER-phagy receptors with structural similarities and nonredundant functions. Whether they respond differentially to the stimulation of ER-phagy is unknown. Here, we describe an activation mechanism unique to FAM134C during starvation. In fed conditions, FAM134C is phosphorylated by casein kinase 2 (CK2) at critical residues flanking the LIR domain. Phosphorylation of these residues negatively affects binding affinity to the autophagy proteins LC3. During starvation, mTORC1 inhibition limits FAM134C phosphorylation by CK2, hence promoting receptor activation and ER-phagy. Using a novel tool to study ER-phagy in vivo and FAM134C knockout mice, we demonstrated the physiological relevance of FAM134C phosphorylation during starvation-induced ER-phagy in liver lipid metabolism. These data provide a mechanistic insight into ER-phagy regulation and an example of autophagy selectivity during starvation. Sci Adv. 2022 ;8(35):eabo1215. http://hdl.handle.net/20.500.12105/15026 36044577 10.1126/sciadv.abo1215 2375-2548 Science advances Phosphorylation of FAM134C by CK2 controls starvation-induced ER-phagy.