title: Translocon component Sec62 acts in endoplasmic reticulum turnover during stress recovery.
abstract: The endoplasmic reticulum (ER) is a site of protein biogenesis in eukaryotic cells. Perturbing ER homeostasis activates stress programs collectively called the unfolded protein response (UPR). The UPR enhances production of ER-resident chaperones and enzymes to reduce the burden of misfolded proteins. On resolution of ER stress, ill-defined, selective autophagic programs remove excess ER components. Here we identify Sec62, a constituent of the translocon complex regulating protein import in the mammalian ER, as an ER-resident autophagy receptor. Sec62 intervenes during recovery from ER stress to selectively deliver ER components to the autolysosomal system for clearance in a series of events that we name recovER-phagy. Sec62 contains a conserved LC3-interacting region in the C-terminal cytosolic domain that is required for its function in recovER-phagy, but is dispensable for its function in the protein translocation machinery. Our results identify Sec62 as a critical molecular component in maintenance and recovery of ER homeostasis.
authors.affiliation: Università della Svizzera italiana, CH-6900 Lugano, Switzerland.|Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.|Graduate School for Cellular and Biomedical Sciences, University of Bern, CH-3000 Bern, Switzerland.
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Fumagalli
authors.affiliation: Università della Svizzera italiana, CH-6900 Lugano, Switzerland.|Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.
authors.forename: Julia
authors.initials: J
authors.lastname: Noack
authors.affiliation: Università della Svizzera italiana, CH-6900 Lugano, Switzerland.|Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.|Department of Biology, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Bergmann
authors.affiliation: Università della Svizzera italiana, CH-6900 Lugano, Switzerland.|Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Cebollero
authors.affiliation: Università della Svizzera italiana, CH-6900 Lugano, Switzerland.|Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.|Department of Biology, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland.
authors.forename: Giorgia Brambilla
authors.initials: GB
authors.lastname: Pisoni
authors.affiliation: Università della Svizzera italiana, CH-6900 Lugano, Switzerland.|Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Fasana
authors.affiliation: Università della Svizzera italiana, CH-6900 Lugano, Switzerland.|Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.|Department of Biology, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Fregno
authors.affiliation: Università della Svizzera italiana, CH-6900 Lugano, Switzerland.|Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.
authors.forename: Carmela
authors.initials: C
authors.lastname: Galli
authors.affiliation: Università della Svizzera italiana, CH-6900 Lugano, Switzerland.|Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.
authors.forename: Marisa
authors.initials: M
authors.lastname: Loi
authors.affiliation: Università della Svizzera italiana, CH-6900 Lugano, Switzerland.|Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Soldà
authors.affiliation: Università della Svizzera italiana, CH-6900 Lugano, Switzerland.|Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.
authors.forename: Rocco
authors.initials: R
authors.lastname: D'Antuono
authors.affiliation: Experimental Imaging Center, San Raffaele Scientific Institute, I-20132 Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Raimondi
authors.affiliation: Medical Biochemistry and Molecular Biology, Saarland University, D-66421 Homburg, Germany.
authors.forename: Martin
authors.identifier: 0000-0002-1482-7020
authors.initials: M
authors.lastname: Jung
authors.affiliation: Medical Biochemistry and Molecular Biology, Saarland University, D-66421 Homburg, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Melnyk
authors.affiliation: Medical Biochemistry and Molecular Biology, Saarland University, D-66421 Homburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schorr
authors.affiliation: Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Schreiber
authors.affiliation: Università della Svizzera italiana, CH-6900 Lugano, Switzerland.|Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Simonelli
authors.affiliation: Università della Svizzera italiana, CH-6900 Lugano, Switzerland.|Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Varani
authors.affiliation: Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Wilson-Zbinden
authors.affiliation: Department of Chemistry, University of Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Zerbe
authors.affiliation: Institute for Genetics, University of Cologne, D-50674 Cologne, Germany.
authors.forename: Kay
authors.identifier: 0000-0002-2289-9083
authors.initials: K
authors.lastname: Hofmann
authors.affiliation: Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Peter
authors.affiliation: Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Manfredo
authors.initials: M
authors.lastname: Quadroni
authors.affiliation: Medical Biochemistry and Molecular Biology, Saarland University, D-66421 Homburg, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Zimmermann
authors.affiliation: Università della Svizzera italiana, CH-6900 Lugano, Switzerland.|Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland.|Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, CH-1015 Lausanne, Switzerland.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Molinari
mesh_terms: D000818:Animals; D001343:Autophagy; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism; D014176:Protein Biosynthesis / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D056811:Unfolded Protein Response / Q000502:physiology
chemical_list: D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; C103676:SEC62 protein, human; C577651:SEC62 protein, mouse