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Control of lysosomal-mediated cell death by the pH-dependent calcium channel RECS1

Authors :
Claudio Hetz
Alvaro Glavic
Philippe Pihán
Amaury Pupo
Suvi Saarnio
Giovanni Quarato
Sandra Sofía Edwards-Jorquera
Diego A. Rodriguez
Daniela De Giorgis
Guido Kroemer
Oliver Kepp
Nicolas Demaurex
Karen Castillo
Eija Jokitalo
Janina Borgonovo
Sabrina Forveille
Amado Carreras-Sureda
Fernanda Lourido
Miguel L. Concha
Paula Nunes-Hasler
Fernanda Lisbona
Douglas R. Green
Anthony Letai
Hery Urra
Alfredo Sagredo
Allan Sauvat
Ramon Latorre
Helena Vihinen
Universidad de Chile = University of Chile [Santiago] (UCHILE)
Université de Genève (UNIGE)
Universidad de Valparaiso [Chile]
Institut Universitaire de France (IUF)
Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)
Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138))
École pratique des hautes études (EPHE)
Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)
Institut Gustave Roussy (IGR)
University of Helsinki
St Jude Children's Research Hospital
Dana-Farber Cancer Institute [Boston]
Brigham & Women’s Hospital [Boston] (BWH)
Harvard Medical School [Boston] (HMS)
Hôpital Européen Georges Pompidou [APHP] (HEGP)
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Chinese Academy of Sciences [Beijing] (CAS)
Karolinska Institutet [Stockholm]
Universidad Catolica Del Maule
Université de Genève = University of Geneva (UNIGE)
Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)
Métabolisme, Cancer et Immunité (CRC - UMR_S 1138)
Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138))
Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE)
Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Helsingin yliopisto = Helsingfors universitet = University of Helsinki
HAL-SU, Gestionnaire
Molecular and Integrative Biosciences Research Programme
Institute of Biotechnology
Electron Microscopy
Biosciences
Source :
Science Advances, Science Advances, American Association for the Advancement of Science (AAAS), 2021, 7 (46), ⟨10.1126/sciadv.abe5469⟩, Science Advances, 2021, 7 (46), ⟨10.1126/sciadv.abe5469⟩, Science advances, Vol. 7, No 46 (2021) P. eabe5469
Publication Year :
2021
Publisher :
HAL CCSD, 2021.

Abstract

Description<br />RECS1, a member of the TMBIM family, triggers lysosomal membrane permeabilization in cells undergoing lysosomal stress.<br />Programmed cell death is regulated by the balance between activating and inhibitory signals. Here, we have identified RECS1 (responsive to centrifugal force and shear stress 1) [also known as TMBIM1 (transmembrane BAX inhibitor motif containing 1)] as a proapoptotic member of the TMBIM family. In contrast to other proteins of the TMBIM family, RECS1 expression induces cell death through the canonical mitochondrial apoptosis pathway. Unbiased screening indicated that RECS1 sensitizes cells to lysosomal perturbations. RECS1 localizes to lysosomes, where it regulates their acidification and calcium content, triggering lysosomal membrane permeabilization. Structural modeling and electrophysiological studies indicated that RECS1 is a pH-regulated calcium channel, an activity that is essential to trigger cell death. RECS1 also sensitizes whole animals to stress in vivo in Drosophila melanogaster and zebrafish models. Our results unveil an unanticipated function for RECS1 as a proapoptotic component of the TMBIM family that ignites cell death programs at lysosomes.

Details

Language :
English
ISSN :
23752548
Database :
OpenAIRE
Journal :
Science Advances, Science Advances, American Association for the Advancement of Science (AAAS), 2021, 7 (46), ⟨10.1126/sciadv.abe5469⟩, Science Advances, 2021, 7 (46), ⟨10.1126/sciadv.abe5469⟩, Science advances, Vol. 7, No 46 (2021) P. eabe5469
Accession number :
edsair.doi.dedup.....8206126f35066a19b6c7861afb35003f
Full Text :
https://doi.org/10.1126/sciadv.abe5469⟩