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

Philippe Pihán; Fernanda Lisbona; Janina Borgonovo; Sandra Edwards-Jorquera; Paula Nunes-Hasler; Karen Castillo; Oliver Kepp; Hery Urra; Suvi Saarnio; Helena Vihinen; Amado Carreras-Sureda; Sabrina Forveille; Allan Sauvat; Daniela De Giorgis; Amaury Pupo; Diego A. Rodríguez; Giovanni Quarato; Alfredo Sagredo; Fernanda Lourido; Anthony Letai; Ramon Latorre; Guido Kroemer; Nicolas Demaurex; Eija Jokitalo; Miguel L. Concha; Álvaro Glavic; Douglas R. Green; Claudio Hetz

doi:10.1126/sciadv.abe5469

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

Philippe Pihán, Fernanda Lisbona, Janina Borgonovo, Sandra Edwards-Jorquera, Paula Nunes-Hasler, Karen Castillo, Oliver Kepp, Hery Urra, Suvi Saarnio, Helena Vihinen, Amado Carreras-Sureda, Sabrina Forveille, Allan Sauvat, Daniela De Giorgis, Amaury Pupo, Diego A. Rodríguez, Giovanni Quarato, Alfredo Sagredo, Fernanda Lourido, Anthony LetaiRamon Latorre, Guido Kroemer, Nicolas Demaurex, Eija Jokitalo, Miguel L. Concha, Álvaro Glavic, Douglas R. Green, Claudio Hetz

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Résumé

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.

langue originale	Anglais
Numéro d'article	eabe5469
journal	Science Advances
Volume	7
Numéro de publication	46
Les DOIs	https://doi.org/10.1126/sciadv.abe5469
état	Publié - 1 nov. 2021

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10.1126/sciadv.abe5469

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Pihán, 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., Rodríguez, D. A., Quarato, G., Sagredo, A., Lourido, F., ... Hetz, C. (2021). Control of lysosomal-mediated cell death by the pH-dependent calcium channel RECS1. Science Advances, 7(46), Article eabe5469. https://doi.org/10.1126/sciadv.abe5469

@article{960bfe1d830e445d988886582932f79f,

title = "Control of lysosomal-mediated cell death by the pH-dependent calcium channel RECS1",

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.",

author = "Philippe Pih{\'a}n and Fernanda Lisbona and Janina Borgonovo and Sandra Edwards-Jorquera and Paula Nunes-Hasler and Karen Castillo and Oliver Kepp and Hery Urra and Suvi Saarnio and Helena Vihinen and Amado Carreras-Sureda and Sabrina Forveille and Allan Sauvat and {De Giorgis}, Daniela and Amaury Pupo and Rodr{\'i}guez, {Diego A.} and Giovanni Quarato and Alfredo Sagredo and Fernanda Lourido and Anthony Letai and Ramon Latorre and Guido Kroemer and Nicolas Demaurex and Eija Jokitalo and Concha, {Miguel L.} and {\'A}lvaro Glavic and Green, {Douglas R.} and Claudio Hetz",

note = "Publisher Copyright: Copyright {\textcopyright} 2021 The Authors.",

year = "2021",

month = nov,

day = "1",

doi = "10.1126/sciadv.abe5469",

language = "English",

volume = "7",

journal = "Science Advances",

issn = "2375-2548",

number = "46",

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Pihán, 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, Rodríguez, DA, Quarato, G, Sagredo, A, Lourido, F, Letai, A, Latorre, R, Kroemer, G, Demaurex, N, Jokitalo, E, Concha, ML, Glavic, Á, Green, DR & Hetz, C 2021, 'Control of lysosomal-mediated cell death by the pH-dependent calcium channel RECS1', Science Advances, VOL. 7, Numéro 46, eabe5469. https://doi.org/10.1126/sciadv.abe5469

TY - JOUR

T1 - Control of lysosomal-mediated cell death by the pH-dependent calcium channel RECS1

AU - Pihán, Philippe

AU - Lisbona, Fernanda

AU - Borgonovo, Janina

AU - Edwards-Jorquera, Sandra

AU - Nunes-Hasler, Paula

AU - Castillo, Karen

AU - Kepp, Oliver

AU - Urra, Hery

AU - Saarnio, Suvi

AU - Vihinen, Helena

AU - Carreras-Sureda, Amado

AU - Forveille, Sabrina

AU - Sauvat, Allan

AU - De Giorgis, Daniela

AU - Pupo, Amaury

AU - Rodríguez, Diego A.

AU - Quarato, Giovanni

AU - Sagredo, Alfredo

AU - Lourido, Fernanda

AU - Letai, Anthony

AU - Latorre, Ramon

AU - Kroemer, Guido

AU - Demaurex, Nicolas

AU - Jokitalo, Eija

AU - Concha, Miguel L.

AU - Glavic, Álvaro

AU - Green, Douglas R.

AU - Hetz, Claudio

PY - 2021/11/1

Y1 - 2021/11/1

N2 - 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.

AB - 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.

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U2 - 10.1126/sciadv.abe5469

DO - 10.1126/sciadv.abe5469

M3 - Article

C2 - 34767445

AN - SCOPUS:85119266007

SN - 2375-2548

VL - 7

JO - Science Advances

JF - Science Advances

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M1 - eabe5469

ER -