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- Giorgia Di Lorenzo
- Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
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- Francescopaolo Iavarone
- Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
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- Marianna Maddaluno
- Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
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- Ana Belén Plata-Gómez
- Metabolism and Cell Signaling Laboratory, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
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- Simone Aureli
- Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Euler Institute, Lugano, Switzerland.
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- Camila Paz Quezada Meza
- Department of Biomedical Sciences, University of Padova, Padova, Italy.
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- Laura Cinque
- Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
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- Alessandro Palma
- Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
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- Alessio Reggio
- Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
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- Carmine Cirillo
- Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
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- Francesca Sacco
- Department of Biology, University of Rome “Tor Vergata”, Rome, Italy.
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- Alexandra Stolz
- Institute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany.
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- Gennaro Napolitano
- Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
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- Oriano Marin
- Department of Biomedical Sciences, University of Padova, Padova, Italy.
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- Lorenzo A. Pinna
- Department of Biomedical Sciences, University of Padova, Padova, Italy.
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- Maria Ruzzene
- Department of Biomedical Sciences, University of Padova, Padova, Italy.
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- Vittorio Limongelli
- Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Euler Institute, Lugano, Switzerland.
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- Alejo Efeyan
- Metabolism and Cell Signaling Laboratory, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
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- Paolo Grumati
- Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
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- Carmine Settembre
- Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
抄録
<jats:p>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.</jats:p>
収録刊行物
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- Science Advances
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Science Advances 8 (35), 2022-09-02
American Association for the Advancement of Science (AAAS)