Document Detail


A yeast BH3-only protein mediates the mitochondrial pathway of apoptosis.
MedLine Citation:
PMID:  21673659     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mitochondrial outer membrane permeabilization is a watershed event in the process of apoptosis, which is tightly regulated by a series of pro- and anti-apoptotic proteins belonging to the BCL-2 family, each characteristically possessing a BCL-2 homology domain 3 (BH3). Here, we identify a yeast protein (Ybh3p) that interacts with BCL-X(L) and harbours a functional BH3 domain. Upon lethal insult, Ybh3p translocates to mitochondria and triggers BH3 domain-dependent apoptosis. Ybh3p induces cell death and disruption of the mitochondrial transmembrane potential via the mitochondrial phosphate carrier Mir1p. Deletion of Mir1p and depletion of its human orthologue (SLC25A3/PHC) abolish stress-induced mitochondrial targeting of Ybh3p in yeast and that of BAX in human cells, respectively. Yeast cells lacking YBH3 display prolonged chronological and replicative lifespans and resistance to apoptosis induction. Thus, the yeast genome encodes a functional BH3 domain that induces cell death through phylogenetically conserved mechanisms.
Authors:
Sabrina Büttner; Doris Ruli; F-Nora Vögtle; Lorenzo Galluzzi; Barbara Moitzi; Tobias Eisenberg; Oliver Kepp; Lukas Habernig; Didac Carmona-Gutierrez; Patrick Rockenfeller; Peter Laun; Michael Breitenbach; Chamel Khoury; Kai-Uwe Fröhlich; Gerald Rechberger; Chris Meisinger; Guido Kroemer; Frank Madeo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-06-14
Journal Detail:
Title:  The EMBO journal     Volume:  30     ISSN:  1460-2075     ISO Abbreviation:  EMBO J.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-20     Completed Date:  2011-09-29     Revised Date:  2011-12-22    
Medline Journal Info:
Nlm Unique ID:  8208664     Medline TA:  EMBO J     Country:  England    
Other Details:
Languages:  eng     Pagination:  2779-92     Citation Subset:  IM    
Affiliation:
Institute of Molecular Biosciences, University of Graz, Graz, Austria.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Apoptosis*
Apoptosis Regulatory Proteins / antagonists & inhibitors,  genetics,  metabolism*
Blotting, Western
Bone Neoplasms / genetics,  metabolism
Cell Cycle
Flow Cytometry
Humans
Immunoprecipitation
Lung Neoplasms / genetics,  metabolism
Membrane Potential, Mitochondrial
Mice
Mitochondria / genetics,  metabolism*
Mitochondrial Proteins / genetics,  metabolism
Molecular Sequence Data
Peptide Fragments / pharmacology*
Phosphate Transport Proteins / genetics,  metabolism
Proto-Oncogene Proteins / pharmacology*
RNA, Messenger / genetics
RNA, Small Interfering / genetics
Reverse Transcriptase Polymerase Chain Reaction
Saccharomyces cerevisiae / genetics,  metabolism*
Saccharomyces cerevisiae Proteins / antagonists & inhibitors,  genetics,  metabolism*
Sequence Homology, Amino Acid
Signal Transduction*
Tumor Cells, Cultured
bcl-2-Associated X Protein / genetics,  metabolism
bcl-X Protein / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Bax protein (53-86); 0/MIR1 protein, S cerevisiae; 0/Mitochondrial Proteins; 0/Peptide Fragments; 0/Phosphate Transport Proteins; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Saccharomyces cerevisiae Proteins; 0/bcl-2-Associated X Protein; 0/bcl-X Protein
Comments/Corrections
Comment In:
EMBO J. 2011 Jul 20;30(14):2754-6   [PMID:  21772325 ]
Cell Death Differ. 2011 Oct;18(10):1543-4   [PMID:  21909117 ]

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