SEPN1-related myopathy depends on the oxidoreductase ERO1A and is druggable with the chemical chaperone TUDCA.

ER stress ERO1 SEPN1 TUDCA core myopathy multi mini-core disease

Journal

Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894

Informations de publication

Date de publication:
19 Feb 2024
Historique:
received: 09 05 2023
revised: 06 12 2023
accepted: 31 01 2024
medline: 25 2 2024
pubmed: 25 2 2024
entrez: 25 2 2024
Statut: aheadofprint

Résumé

Selenoprotein N (SEPN1) is a protein of the endoplasmic reticulum (ER) whose inherited defects originate SEPN1-related myopathy (SEPN1-RM). Here, we identify an interaction between SEPN1 and the ER-stress-induced oxidoreductase ERO1A. SEPN1 and ERO1A, both enriched in mitochondria-associated membranes (MAMs), are involved in the redox regulation of proteins. ERO1A depletion in SEPN1 knockout cells restores ER redox, re-equilibrates short-range MAMs, and rescues mitochondrial bioenergetics. ERO1A knockout in a mouse background of SEPN1 loss blunts ER stress and improves multiple MAM functions, including Ca

Identifiants

DOI: 10.1016/j.xcrm.2024.101439 PMID: 38402623
pubmed: 38402623
pii: S2666-3791(24)00062-4
doi: 10.1016/j.xcrm.2024.101439
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

101439

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Serena Germani (S)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy; Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.

Andrew Tri Van Ho (AT)

Basic and Translational Myology Laboratory, Université Paris, BFA, UMR 8251, CNRS, 75013 Paris, France.

Alessandro Cherubini (A)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Ersilia Varone (E)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Alexander Chernorudskiy (A)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Giorgia Maria Renna (GM)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Stefano Fumagalli (S)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Marco Gobbi (M)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Jacopo Lucchetti (J)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Marco Bolis (M)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy; Bioinformatics Core Unit, Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland.

Luca Guarrera (L)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Ilaria Craparotta (I)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Giorgia Rastelli (G)

CAST, Center for Advanced Studies and Technology & DNICS, Department of Neuroscience, Imaging and Clinical Sciences, University G. D'Annunzio of Chieti-Pescara, 66100 Chieti, Italy.

Giorgia Piccoli (G)

Department of Biomedical Sciences, University of Padua, Padua, Italy.

Cosimo de Napoli (C)

Department of Biomedical Sciences, University of Padua, Padua, Italy.

Leonardo Nogara (L)

Department of Biomedical Sciences, University of Padua, Padua, Italy; Department of Pharmaceutical Sciences, University of Padova, Padova, Italy.

Elena Poggio (E)

Department of Biology, University of Padova, Padova, Italy.

Marisa Brini (M)

Department of Pharmaceutical Sciences, University of Padova, Padova, Italy; Department of Biology, University of Padova, Padova, Italy; Study Center for Neurodegeneration (CESNE), University of Padova, Padova, Italy.

Angela Cattaneo (A)

Cogentech SRL Benefit Corporation, 20139 Milan, Italy.

Angela Bachi (A)

IFOM-ETS AIRC Institute of Molecular Oncology, Milan, Italy.

Thomas Simmen (T)

Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

Tito Calì (T)

Department of Biomedical Sciences, University of Padua, Padua, Italy; Study Center for Neurodegeneration (CESNE), University of Padova, Padova, Italy; Padova Neuroscience Center, University of Padova, Padova, Italy.

Susana Quijano-Roy (S)

APHP-Université Paris-Saclay, Reference Center for Neuromuscular Disorders Nord-Est-Ile de France, FILNEMUS, ERN-Euro-NMD, Creteil, France; Pediatric Neurology and ICU Department, DMU Santé Enfant Adolescent (SEA), Raymond Poincaré University Hospital, Garches, France.

Simona Boncompagni (S)

CAST, Center for Advanced Studies and Technology & DNICS, Department of Neuroscience, Imaging and Clinical Sciences, University G. D'Annunzio of Chieti-Pescara, 66100 Chieti, Italy.

Bert Blaauw (B)

Department of Biomedical Sciences, University of Padua, Padua, Italy; Venetian Institute of Molecular Medicine, Padova, Italy. Electronic address: bert.blaauw@unipd.it.

Ana Ferreiro (A)

Basic and Translational Myology Laboratory, Université Paris, BFA, UMR 8251, CNRS, 75013 Paris, France; APHP, Reference Center for Neuromuscular Disorders Nord-Est-Ile de France, Neuromyology Department, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. Electronic address: ana.b.ferreiro@gmail.com.

Ester Zito (E)

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy. Electronic address: ester.zito@marionegri.it.

Classifications MeSH