Journal article
Two isoforms of PSAP/MTCH1 share two proapoptotic domains and multiple internal signals for import into the mitochondrial outer membrane
American Journal of Physiology: Cell Physiology, v 293(4), pp C1347-C1361
01 Oct 2007
PMID: 17670888
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Presenilin 1-associated protein ( PSAP) was first identified as a protein that interacts with presenilin 1. It was later reported that PSAP is a mitochondrial protein that induces apoptosis when overexpressed in cultured cells. PSAP is also known as mitochondrial carrier homolog 1 (Mtch1). In this study, we show that there are two proapoptotic PSAP isoforms generated by alternative splicing that differ in the length of a hydrophilic loop located between two predicted transmembrane domains. Using RT-PCR and Western blot assays, we determined that both isoforms are expressed in human and rat tissues as well as in culture cells. Our results indicate that PSAP is an integral mitochondrial outer membrane protein, although it contains a mitochondrial carrier domain conserved in several inner membrane carriers, which partially overlaps one of the predicted transmembrane segments. Deletion of this transmembrane segment impairs mitochondrial import of PSAP. Replacement of this segment with each of two transmembrane domains, with opposite membrane orientations, from an unrelated protein indicated that one of them allowed mitochondrial localization of the PSAP mutant, whereas the other one did not. Our interpretation of these results is that PSAP contains multiple mitochondrial targeting motifs dispersed along the protein but that a transmembrane domain in the correct position and orientation is necessary for membrane insertion. The amino acid sequence within this transmembrane domain may also be important. Furthermore, two independent regions in the amino terminal side of the protein are responsible for its proapoptotic activity. Possible implications of these findings in PSAP function are discussed.
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Details
- Title
- Two isoforms of PSAP/MTCH1 share two proapoptotic domains and multiple internal signals for import into the mitochondrial outer membrane
- Creators
- Violeta Lamarca - Universidad de ZaragozaAntonio Sanz-Clemente - Universidad de ZaragozaRosaura Perez-Pe - Universidad de ZaragozaMaria Jose Martinez-Lorenzo - Universidad de ZaragozaNabil Halaihel - Universidad de ZaragozaPedro Muniesa - Universidad de ZaragozaJose A. Carrodeguas - Universidad de Zaragoza
- Publication Details
- American Journal of Physiology: Cell Physiology, v 293(4), pp C1347-C1361
- Publisher
- Amer Physiological Soc
- Number of pages
- 15
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000250052400017
- Scopus ID
- 2-s2.0-35048822838
- Other Identifier
- 991020100200504721
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- Web of Science research areas
- Cell Biology
- Physiology