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dc.contributor.authorDi Lorenzo, Giorgia
dc.contributor.authorIavarone, Francescopaolo
dc.contributor.authorMaddaluno, Marianna
dc.contributor.authorPlata-Gómez, Ana Belén
dc.contributor.authorAureli, Simone
dc.contributor.authorQuezada Meza, Camila Paz
dc.contributor.authorCinque, Laura
dc.contributor.authorPalma, Alessandro
dc.contributor.authorReggio, Alessio
dc.contributor.authorCirillo, Carmine
dc.contributor.authorSacco, Francesca
dc.contributor.authorStolz, Alexandra
dc.contributor.authorNapolitano, Gennaro
dc.contributor.authorMarin, Oriano
dc.contributor.authorPinna, Lorenzo A
dc.contributor.authorRuzzene, Maria
dc.contributor.authorLimongelli, Vittorio
dc.contributor.authorEfeyan, Alejo 
dc.contributor.authorGrumati, Paolo
dc.contributor.authorSettembre, Carmine
dc.contributor.authorPinna, Lorenzo A.
dc.identifier.citationSci Adv. 2022 ;8(35):eabo1215.es_ES
dc.description.abstractSelective 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.es_ES
dc.description.sponsorshipWe thank G. Diez Roux and P. Ashley-Norman for critical reading of the manuscript. We thank the microscopy, MS, advanced histopathology, and FACS facilities at TIGEM Institute. We thank E. Nusco for helping us with AAV injections. Funding: This work was supported by European Research Council (ERC) (714551), Telethon intramural grants, and Associazione Italiana per la Ricerca sul Cancro (AIRC) (IG 2015 Id 17717) (to C.S.) and Telethon Foundation (TMPGCBX16TT), AFM Telethon (Trampoline Grant), and AIRC (MFAG-2020-24856) (to P.G.). G.D.L. is a recipient of AIRC fellowship “Francesco Alicino” (25407). V.L. acknowledges funding from the ERC (101001784), the Italian MIUR-PRIN 2017 (2017FJZZRC), and the Swiss National Supercomputing Center (CSCS) (project ID u8). The work of A.S. was supported by the German Research Foundation DFG (SFB1177/2 and WO210/20-2) and the Dr. Rolf M. Schwiete Stiftung (13/2017). A.E. is supported by the RETOS projects Programme of Spanish Ministry of Science, Innovation and Universities, Spanish State Research Agency (grants SAF2015-67538-R and PID2019-104012RB-I00), and the ERC (638891). A.B.P.-G. is a recipient of Ph.D. fellowship from MICIU/AEI (BES-2017-081381). A.R. is a recipient of Umberto Veronesi Foundation postdoctoral fellowship. Author contributions: G.D.L. and F.I. performed most of the experiments. F.I. and A.B.P.-G. performed in vivo experiments. M.M. performed mutagenesis experiments. S.A. and V.L. performed LC3-FAM134C binding analysis. C.P.Q.M. performed in vitro phosphorylation assays. L.C. analyzed CK2 substrate phosphorylation. F.S., A.P., C.C., and A.S. analyzed proteomic data. G.N. provided critical suggestions. A.R. performed proteomic experiments. A.E. supervised in vivo experiments. M.R., L.A.P., and O.M. supervised CK2 experiments. C.S. designed the study. P.G. and C.S. conceived and supervised the experiments. C.S., P.G., V.L., and M.R. wrote the paper. G.D.L. and F.I. prepared the figures. All the authors read the manuscript. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.es_ES
dc.publisherAmerican Association for the Advancement of Science (AAAS) es_ES
dc.titlePhosphorylation of FAM134C by CK2 controls starvation-induced ER-phagy.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.contributor.funderEuropean Research Council es_ES
dc.contributor.funderItalian Association for Cancer Research es_ES
dc.contributor.funderSwiss National Supercomputing Center (CSCS)es_ES
dc.contributor.funderDeutsche Forschungsgemeinschaft (Alemania) es_ES
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (España) es_ES
dc.identifier.journalScience advanceses_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Metabolismo y Señalización Celulares_ES
dc.rights.accessRightsopen accesses_ES

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