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

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dc.contributor.author Pihan, Philippe
dc.contributor.author Lisbona, Fernanda
dc.contributor.author Borgonovo, Janina
dc.contributor.author Edwards-Jorquera, Sandra
dc.contributor.author Nunes-Hasler, Paula
dc.contributor.author Castillo, Karen
dc.contributor.author Kepp, Oliver
dc.contributor.author Urra, Hery
dc.contributor.author Saarnio, Suvi
dc.contributor.author Vihinen, Helena
dc.contributor.author Carreras-Sureda, Amado
dc.contributor.author Forveille, Sabrina
dc.contributor.author Sauvat, Allan
dc.contributor.author De Giorgis, Daniela
dc.contributor.author Pupo, Amaury
dc.contributor.author Rodriguez, Diego A.
dc.contributor.author Quarato, Giovanni
dc.contributor.author Sagredo, Alfredo
dc.contributor.author Lourido, Fernanda
dc.contributor.author Letai, Anthony
dc.contributor.author Latorre, Ramon
dc.contributor.author Kroemer, Guido
dc.contributor.author Demaurex, Nicolas
dc.contributor.author Jokitalo, Eija
dc.contributor.author Concha, Miguel L.
dc.contributor.author Glavic, Alvaro
dc.contributor.author Green, Douglas R.
dc.contributor.author Hetz, Claudio
dc.date.accessioned 2022-01-07T14:13:06Z
dc.date.available 2022-01-07T14:13:06Z
dc.date.issued 2021-11
dc.identifier.citation Pihan , P , Lisbona , F , Borgonovo , J , Edwards-Jorquera , S , Nunes-Hasler , P , Castillo , K , Kepp , O , Urra , H , Saarnio , S , Vihinen , H , Carreras-Sureda , A , Forveille , S , Sauvat , A , De Giorgis , D , Pupo , A , Rodriguez , D A , Quarato , G , Sagredo , A , Lourido , F , Letai , A , Latorre , R , Kroemer , G , Demaurex , N , Jokitalo , E , Concha , M L , Glavic , A , Green , D R & Hetz , C 2021 , ' Control of lysosomal-mediated cell death by the pH-dependent calcium channel RECS1 ' , Science Advances , vol. 7 , no. 46 , 5469 . https://doi.org/10.1126/sciadv.abe5469
dc.identifier.other PURE: 171703554
dc.identifier.other PURE UUID: fa27a902-8fc8-44c3-9db5-90df92f3cfd0
dc.identifier.other WOS: 000720344200001
dc.identifier.other ORCID: /0000-0003-3862-9237/work/105908234
dc.identifier.other ORCID: /0000-0002-4159-6934/work/105911584
dc.identifier.uri http://hdl.handle.net/10138/338345
dc.description.abstract 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. en
dc.format.extent 18
dc.language.iso eng
dc.relation.ispartof Science Advances
dc.rights cc_by_nc
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject UNFOLDED PROTEIN RESPONSE
dc.subject ANTI-APOPTOTIC PROTEINS
dc.subject BAX INHIBITOR-1
dc.subject MEMBRANE PERMEABILIZATION
dc.subject NEGATIVE REGULATOR
dc.subject STRESS
dc.subject ER
dc.subject BI-1
dc.subject CA2+
dc.subject FLUORESCENCE
dc.subject 1182 Biochemistry, cell and molecular biology
dc.title Control of lysosomal-mediated cell death by the pH-dependent calcium channel RECS1 en
dc.type Article
dc.contributor.organization Molecular and Integrative Biosciences Research Programme
dc.contributor.organization Institute of Biotechnology
dc.contributor.organization Electron Microscopy
dc.contributor.organization Biosciences
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1126/sciadv.abe5469
dc.relation.issn 2375-2548
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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