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

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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

Title: Control of lysosomal-mediated cell death by the pH-dependent calcium channel RECS1
Author: 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
Contributor organization: Molecular and Integrative Biosciences Research Programme
Institute of Biotechnology
Electron Microscopy
Biosciences
Date: 2021-11
Language: eng
Number of pages: 18
Belongs to series: Science Advances
ISSN: 2375-2548
DOI: https://doi.org/10.1126/sciadv.abe5469
URI: http://hdl.handle.net/10138/338345
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.
Subject: UNFOLDED PROTEIN RESPONSE
ANTI-APOPTOTIC PROTEINS
BAX INHIBITOR-1
MEMBRANE PERMEABILIZATION
NEGATIVE REGULATOR
STRESS
ER
BI-1
CA2+
FLUORESCENCE
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by_nc
Usage restriction: openAccess
Self-archived version: publishedVersion


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