Phosphorylation of FAM134C by CK2 controls starvation-induced ER-phagy-Reference-Cited by-同舟云学术

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

Published:2022-09-02 Issue:35 Volume:8 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Di Lorenzo Giorgia¹^ORCID,Iavarone Francescopaolo¹^ORCID,Maddaluno Marianna¹^ORCID,Plata-Gómez Ana Belén²^ORCID,Aureli Simone³^ORCID,Quezada Meza Camila Paz⁴^ORCID,Cinque Laura¹⁵^ORCID,Palma Alessandro¹^ORCID,Reggio Alessio¹^ORCID,Cirillo Carmine¹^ORCID,Sacco Francesca⁶^ORCID,Stolz Alexandra⁷⁸^ORCID,Napolitano Gennaro¹⁹^ORCID,Marin Oriano⁴^ORCID,Pinna Lorenzo A.⁴¹⁰^ORCID,Ruzzene Maria⁴¹⁰^ORCID,Limongelli Vittorio³¹¹^ORCID,Efeyan Alejo²^ORCID,Grumati Paolo¹⁵^ORCID,Settembre Carmine¹⁵^ORCID

Affiliation:

1. Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.

2. Metabolism and Cell Signaling Laboratory, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

3. Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Euler Institute, Lugano, Switzerland.

4. Department of Biomedical Sciences, University of Padova, Padova, Italy.

5. Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.

6. Department of Biology, University of Rome “Tor Vergata”, Rome, Italy.

7. Institute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany.

8. Buchmann Institute for Molecular Life Sciences (BMLS), Goethe University, Frankfurt am Main, Germany.

9. Department of Translational Medicine, Federico II University, Naples, Italy.

10. CNR Neuroscience Institute, Padova, Italy.

11. Department of Pharmacy, Federico II University, Naples, Italy.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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