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PMID: 10613907 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Adenine nucleotide translocase-1, a component of the permeability transition pore, can dominantly induce apoptosis.

The Journal of cell biology ·Vol. 147 ·No. 7 ·1999-12-27 ·Pages 1493-502

Bauer MK, Schubert A, Rocks O, Grimm S

Abstract

Here, we describe the isolation of adenine nucleotide translocase-1 (ANT-1) in a screen for dominant, apoptosis-inducing genes. ANT-1 is a component of the mitochondrial permeability transition complex, a protein aggregate connecting the inner with the outer mitochondrial membrane that has recently been implicated in apoptosis. ANT-1 expression led to all features of apoptosis, such as phenotypic alterations, collapse of the mitochondrial membrane potential, cytochrome c release, caspase activation, and DNA degradation. Both point mutations that impair ANT-1 in its known activity to transport ADP and ATP as well as the NH(2)-terminal half of the protein could still induce apoptosis. Interestingly, ANT-2, a highly homologous protein could not lead to cell death, demonstrating the specificity of the signal for apoptosis induction. In contrast to Bax, a proapoptotic Bcl-2 gene, ANT-1 was unable to elicit a form of cell death in yeast. This and the observed repression of apoptosis by the ANT-1-interacting protein cyclophilin D suggest that the suicidal effect of ANT-1 is mediated by specific protein-protein interactions within the permeability transition pore.

MeSH Terms
Animals Apoptosis/drug effects,physiology Cell Death/physiology Cell Division/physiology Cell Line Cricetinae Cyclophilin D Cyclophilins Humans Immunophilins/physiology Intracellular Membranes/enzymology,physiology Membrane Potentials/physiology Mice Mitochondria/enzymology,physiology Mitochondrial ADP, ATP Translocases/antagonists & inhibitors,physiology Peptide Fragments/physiology Permeability Saccharomyces cerevisiae/cytology,growth & development
Chemicals
Cyclophilin D PPIF protein, mouse Peptide Fragments Mitochondrial ADP, ATP Translocases Cyclophilins Immunophilins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Bauer M K
Max-Planck-Institute for Biochemistry, 82152 Martinsried, Germany.
Schubert A
Rocks O
Grimm S
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.147.7.1493
Published
1999-12-27
Pages
1493-502
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2174250
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.147.7.1493 PMC Full Text View journal details
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