Exposure of any of two proapoptotic domains of presenilin 1-associated protein/mitochondrial carrier homolog 1 on the surface of mitochondria is sufficient for induction of apoptosis in a Bax/Bak-independent manner

Violeta Lamarca; Isabel Marzo; Antonio Sanz-Clemente; José A. Carrodeguas

doi:10.1016/j.ejcb.2008.02.004

Exposure of any of two proapoptotic domains of presenilin 1-associated protein/mitochondrial carrier homolog 1 on the surface of mitochondria is sufficient for induction of apoptosis in a Bax/Bak-independent manner

Violeta Lamarca, Isabel Marzo, Antonio Sanz-Clemente, José A. Carrodeguas^*

^*Corresponding author for this work

Pharmacology

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Presenilin 1-associated protein/mitochondrial carrier homolog 1 (PSAP/Mtch1) is a proapoptotic outer mitochondrial membrane protein first identified as a presenilin 1-associated protein. The mechanism by which it induces apoptosis upon overexpression in cultured cells is so far unknown. We had previously reported that deletion of two independent regions of PSAP/Mtch1 is required to prevent apoptosis. We now report that mitochondrial targeting of the region containing both proapoptotic domains, or any of them independently, to the outer membrane is sufficient to induce apoptosis. On the other hand, targeting of that region to the surface of the endoplasmic reticulum does not induce apoptosis, indicating that attachment of those domains to the outer mitochondrial membrane, and not just cytosolic exposure, is a requisite for apoptosis. Overexpression of PSAP/Mtch1 in cultured cells causes mitochondrial depolarization and apoptosis that does not depend on Bax or Bak, since apoptosis is induced in mouse embryonic fibroblasts lacking these two proteins. Our results suggest that apoptosis induced by PSAP/Mtch1 likely involves the permeability transition pore.

Original language	English (US)
Pages (from-to)	325-334
Number of pages	10
Journal	European journal of cell biology
Volume	87
Issue number	5
DOIs	https://doi.org/10.1016/j.ejcb.2008.02.004
State	Published - May 21 2008

Funding

We thank María Royo and María José Martínez for excellent technical assistance and help, respectively, with the confocal microscope, and the I+CS for access to the microscope. We thank all BIFI members for support, especially Dr. Javier Sancho and Dr. José Luis Alonso. We thank Cristina Muñoz Pinedo for the gift of wild-type and DKO MEFs. We thank Dr. Javier Naval for access to the cytometer and for critical discussions, people in his lab for their help, and Julián Pardo for critical discussions. J.A.C. specially thanks Dr. Pascual López Buesa for strong moral support. V. Lamarca is a predoctoral fellow of the Diputación General de Aragón (B056/2004). J.A. Carrodeguas was a researcher of the Ramón y Cajal program and is currently funded by the Ministerio de Educación y Ciencia and BIFI through the University of Zaragoza. This work was funded by grants BMC-2003-05265 from the former Ministerio de Ciencia y Tecnología and BFU2006-07026 from the Ministerio de Educación y Ciencia to J.A. Carrodeguas, and by FEDER.

Keywords

Alzheimer
Apoptosis
Bak
Bax
Mimp/Mtch2
Mitochondria
Outer membrane
PSAP/Mtch1
Permeability transition
Presenilin

ASJC Scopus subject areas

Pathology and Forensic Medicine
Histology
Cell Biology

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Lamarca, V., Marzo, I., Sanz-Clemente, A., & Carrodeguas, J. A. (2008). Exposure of any of two proapoptotic domains of presenilin 1-associated protein/mitochondrial carrier homolog 1 on the surface of mitochondria is sufficient for induction of apoptosis in a Bax/Bak-independent manner. European journal of cell biology, 87(5), 325-334. https://doi.org/10.1016/j.ejcb.2008.02.004

@article{cb1ea54b049d44a8953e0fafdae4dd4e,

title = "Exposure of any of two proapoptotic domains of presenilin 1-associated protein/mitochondrial carrier homolog 1 on the surface of mitochondria is sufficient for induction of apoptosis in a Bax/Bak-independent manner",

abstract = "Presenilin 1-associated protein/mitochondrial carrier homolog 1 (PSAP/Mtch1) is a proapoptotic outer mitochondrial membrane protein first identified as a presenilin 1-associated protein. The mechanism by which it induces apoptosis upon overexpression in cultured cells is so far unknown. We had previously reported that deletion of two independent regions of PSAP/Mtch1 is required to prevent apoptosis. We now report that mitochondrial targeting of the region containing both proapoptotic domains, or any of them independently, to the outer membrane is sufficient to induce apoptosis. On the other hand, targeting of that region to the surface of the endoplasmic reticulum does not induce apoptosis, indicating that attachment of those domains to the outer mitochondrial membrane, and not just cytosolic exposure, is a requisite for apoptosis. Overexpression of PSAP/Mtch1 in cultured cells causes mitochondrial depolarization and apoptosis that does not depend on Bax or Bak, since apoptosis is induced in mouse embryonic fibroblasts lacking these two proteins. Our results suggest that apoptosis induced by PSAP/Mtch1 likely involves the permeability transition pore.",

keywords = "Alzheimer, Apoptosis, Bak, Bax, Mimp/Mtch2, Mitochondria, Outer membrane, PSAP/Mtch1, Permeability transition, Presenilin",

author = "Violeta Lamarca and Isabel Marzo and Antonio Sanz-Clemente and Carrodeguas, {Jos{\'e} A.}",

note = "Funding Information: We thank Mar{\'i}a Royo and Mar{\'i}a Jos{\'e} Mart{\'i}nez for excellent technical assistance and help, respectively, with the confocal microscope, and the I+CS for access to the microscope. We thank all BIFI members for support, especially Dr. Javier Sancho and Dr. Jos{\'e} Luis Alonso. We thank Cristina Mu{\~n}oz Pinedo for the gift of wild-type and DKO MEFs. We thank Dr. Javier Naval for access to the cytometer and for critical discussions, people in his lab for their help, and Juli{\'a}n Pardo for critical discussions. J.A.C. specially thanks Dr. Pascual L{\'o}pez Buesa for strong moral support. V. Lamarca is a predoctoral fellow of the Diputaci{\'o}n General de Arag{\'o}n (B056/2004). J.A. Carrodeguas was a researcher of the Ram{\'o}n y Cajal program and is currently funded by the Ministerio de Educaci{\'o}n y Ciencia and BIFI through the University of Zaragoza. This work was funded by grants BMC-2003-05265 from the former Ministerio de Ciencia y Tecnolog{\'i}a and BFU2006-07026 from the Ministerio de Educaci{\'o}n y Ciencia to J.A. Carrodeguas, and by FEDER.",

year = "2008",

month = may,

day = "21",

doi = "10.1016/j.ejcb.2008.02.004",

language = "English (US)",

volume = "87",

pages = "325--334",

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Lamarca, V, Marzo, I, Sanz-Clemente, A & Carrodeguas, JA 2008, 'Exposure of any of two proapoptotic domains of presenilin 1-associated protein/mitochondrial carrier homolog 1 on the surface of mitochondria is sufficient for induction of apoptosis in a Bax/Bak-independent manner', European journal of cell biology, vol. 87, no. 5, pp. 325-334. https://doi.org/10.1016/j.ejcb.2008.02.004

Exposure of any of two proapoptotic domains of presenilin 1-associated protein/mitochondrial carrier homolog 1 on the surface of mitochondria is sufficient for induction of apoptosis in a Bax/Bak-independent manner. / Lamarca, Violeta; Marzo, Isabel; Sanz-Clemente, Antonio et al.
In: European journal of cell biology, Vol. 87, No. 5, 21.05.2008, p. 325-334.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Exposure of any of two proapoptotic domains of presenilin 1-associated protein/mitochondrial carrier homolog 1 on the surface of mitochondria is sufficient for induction of apoptosis in a Bax/Bak-independent manner

AU - Lamarca, Violeta

AU - Marzo, Isabel

AU - Sanz-Clemente, Antonio

AU - Carrodeguas, José A.

N1 - Funding Information: We thank María Royo and María José Martínez for excellent technical assistance and help, respectively, with the confocal microscope, and the I+CS for access to the microscope. We thank all BIFI members for support, especially Dr. Javier Sancho and Dr. José Luis Alonso. We thank Cristina Muñoz Pinedo for the gift of wild-type and DKO MEFs. We thank Dr. Javier Naval for access to the cytometer and for critical discussions, people in his lab for their help, and Julián Pardo for critical discussions. J.A.C. specially thanks Dr. Pascual López Buesa for strong moral support. V. Lamarca is a predoctoral fellow of the Diputación General de Aragón (B056/2004). J.A. Carrodeguas was a researcher of the Ramón y Cajal program and is currently funded by the Ministerio de Educación y Ciencia and BIFI through the University of Zaragoza. This work was funded by grants BMC-2003-05265 from the former Ministerio de Ciencia y Tecnología and BFU2006-07026 from the Ministerio de Educación y Ciencia to J.A. Carrodeguas, and by FEDER.

PY - 2008/5/21

Y1 - 2008/5/21

N2 - Presenilin 1-associated protein/mitochondrial carrier homolog 1 (PSAP/Mtch1) is a proapoptotic outer mitochondrial membrane protein first identified as a presenilin 1-associated protein. The mechanism by which it induces apoptosis upon overexpression in cultured cells is so far unknown. We had previously reported that deletion of two independent regions of PSAP/Mtch1 is required to prevent apoptosis. We now report that mitochondrial targeting of the region containing both proapoptotic domains, or any of them independently, to the outer membrane is sufficient to induce apoptosis. On the other hand, targeting of that region to the surface of the endoplasmic reticulum does not induce apoptosis, indicating that attachment of those domains to the outer mitochondrial membrane, and not just cytosolic exposure, is a requisite for apoptosis. Overexpression of PSAP/Mtch1 in cultured cells causes mitochondrial depolarization and apoptosis that does not depend on Bax or Bak, since apoptosis is induced in mouse embryonic fibroblasts lacking these two proteins. Our results suggest that apoptosis induced by PSAP/Mtch1 likely involves the permeability transition pore.

AB - Presenilin 1-associated protein/mitochondrial carrier homolog 1 (PSAP/Mtch1) is a proapoptotic outer mitochondrial membrane protein first identified as a presenilin 1-associated protein. The mechanism by which it induces apoptosis upon overexpression in cultured cells is so far unknown. We had previously reported that deletion of two independent regions of PSAP/Mtch1 is required to prevent apoptosis. We now report that mitochondrial targeting of the region containing both proapoptotic domains, or any of them independently, to the outer membrane is sufficient to induce apoptosis. On the other hand, targeting of that region to the surface of the endoplasmic reticulum does not induce apoptosis, indicating that attachment of those domains to the outer mitochondrial membrane, and not just cytosolic exposure, is a requisite for apoptosis. Overexpression of PSAP/Mtch1 in cultured cells causes mitochondrial depolarization and apoptosis that does not depend on Bax or Bak, since apoptosis is induced in mouse embryonic fibroblasts lacking these two proteins. Our results suggest that apoptosis induced by PSAP/Mtch1 likely involves the permeability transition pore.

KW - Alzheimer

KW - Apoptosis

KW - Bak

KW - Bax

KW - Mimp/Mtch2

KW - Mitochondria

KW - Outer membrane

KW - PSAP/Mtch1

KW - Permeability transition

KW - Presenilin

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UR - http://www.scopus.com/inward/citedby.url?scp=42149110337&partnerID=8YFLogxK

U2 - 10.1016/j.ejcb.2008.02.004

DO - 10.1016/j.ejcb.2008.02.004

M3 - Article

C2 - 18375015

AN - SCOPUS:42149110337

SN - 0171-9335

VL - 87

SP - 325

EP - 334

JO - European journal of cell biology

JF - European journal of cell biology

IS - 5

ER -

Exposure of any of two proapoptotic domains of presenilin 1-associated protein/mitochondrial carrier homolog 1 on the surface of mitochondria is sufficient for induction of apoptosis in a Bax/Bak-independent manner

Abstract

Funding

Keywords

ASJC Scopus subject areas

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