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

Show simple item record Pihan, Philippe Lisbona, Fernanda Borgonovo, Janina Edwards-Jorquera, Sandra Nunes-Hasler, Paula Castillo, Karen Kepp, Oliver Urra, Hery Saarnio, Suvi Vihinen, Helena Carreras-Sureda, Amado Forveille, Sabrina Sauvat, Allan De Giorgis, Daniela Pupo, Amaury Rodriguez, Diego A. Quarato, Giovanni Sagredo, Alfredo Lourido, Fernanda Letai, Anthony Latorre, Ramon Kroemer, Guido Demaurex, Nicolas Jokitalo, Eija Concha, Miguel L. Glavic, Alvaro Green, Douglas R. Hetz, Claudio 2022-01-07T14:13:06Z 2022-01-07T14:13:06Z 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 .
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.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 BAX INHIBITOR-1
dc.subject STRESS
dc.subject ER
dc.subject BI-1
dc.subject CA2+
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.issn 2375-2548
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

Files in this item

Total number of downloads: Loading...

Files Size Format View
sciadv.abe5469.pdf 11.07Mb PDF View/Open

This item appears in the following Collection(s)

Show simple item record