Journal article

Phosphorylation of FAM134C by CK2 controls starvation-induced ER-phagy

  • Di Lorenzo, Giorgia Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy
  • Iavarone, Francescopaolo Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy
  • Maddaluno, Marianna Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy
  • Plata-Gómez, Ana Belén Metabolism and Cell Signaling Laboratory, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
  • Aureli, Simone ORCID Euler Institute (EUL), Università della Svizzera italiana, Switzerland
  • Quezada Meza, Camila Paz Department of Biomedical Sciences, University of Padova, Padova, Italy
  • Cinque, Laura Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy
  • Palma, Alessandro Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy
  • Reggio, Alessio Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy
  • Cirillo, Carmine Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy
  • Sacco, Francesca Department of Biology, University of Rome “Tor Vergata”, Rome, Italy
  • Stolz, Alexandra Institute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany ; Buchmann Institute for Molecular Life Sciences (BMLS), Goethe University, Frankfurt am Main, Germany
  • Napolitano, Gennaro Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy
  • Marin, Oriano Department of Biomedical Sciences, University of Padova, Padova, Italy
  • Pinna, Lorenzo A. Department of Biomedical Sciences, University of Padova, Padova, Italy ; CNR Neuroscience Institute, Padova, Italy
  • Ruzzene, Maria Department of Biomedical Sciences, University of Padova, Padova, Italy ; CNR Neuroscience Institute, Padova, Italy
  • Limongelli, Vittorio ORCID Euler Institute (EUL), Università della Svizzera italiana, Switzerland ; Department of Pharmacy, Federico II University, Naples, Italy
  • Efeyan, Alejo Metabolism and Cell Signaling Laboratory, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
  • Grumati, Paolo Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy ; Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
  • Settembre, Carmine Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy ; Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
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  • 2022
Published in:
  • Science advances. - 2022, vol. 8, no. 35, p. eabo1215
English 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.
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  • English
Classification
Medicine
License
CC BY
Open access status
gold
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Persistent URL
https://n2t.net/ark:/12658/srd1328303
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