Journal article
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, v 87(5), pp 325-334
2008
PMID: 18375015
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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.
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Details
- 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
- Creators
- Violeta Lamarca - Universidad de ZaragozaIsabel Marzo - Universidad de ZaragozaAntonio Sanz-Clemente - Universidad de ZaragozaJosé A. Carrodeguas - Universidad de Zaragoza
- Publication Details
- European journal of cell biology, v 87(5), pp 325-334
- Publisher
- Elsevier GmbH
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000256138600006
- Scopus ID
- 2-s2.0-42149110337
- Other Identifier
- 991020099179204721
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- Web of Science research areas
- Cell Biology