2026-04-29T00:59:53Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/150262024-11-29T20:11:17Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
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.
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Italian Association for Cancer Research
funder
Deutsche Forschungsgemeinschaft (Alemania)
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Swiss National Supercomputing Center (CSCS)
2022-10-03T12:15:35Z
2022-10-03T12:15:35Z
2022-09-02
Sci Adv. 2022 ;8(35):eabo1215.
http://hdl.handle.net/20.500.12105/15026
36044577
10.1126/sciadv.abo1215
2375-2548
Science advances
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.
eng
Phosphorylation of FAM134C by CK2 controls starvation-induced ER-phagy.
journal article
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PhosphorylationofFAM134CbyCK2_2022.pdf
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PhosphorylationofFAM134CbyCK2_2022.pdf.txt