Adenine nucleotide translocase-1, a component of the permeability transition pore, can dominantly induce apoptosis.
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.
Bauer
M K
MK
Max-Planck-Institute for Biochemistry, 82152 Martinsried, Germany.
Schubert
A
A
Rocks
O
O
Grimm
S
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D006224:Cricetinae; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins; D006801:Humans; D020104:Immunophilins / Q000502:physiology; D007425:Intracellular Membranes / Q000201:enzymology* / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000201:enzymology* / Q000502:physiology; D000226:Mitochondrial ADP, ATP Translocases / Q000037:antagonists & inhibitors / Q000502:physiology*; D010446:Peptide Fragments / Q000502:physiology; D010539:Permeability; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000254:growth & development
D000081406:Peptidyl-Prolyl Isomerase F; C000631446:PPIF protein, mouse; D010446:Peptide Fragments; D000226:Mitochondrial ADP, ATP Translocases; D021983:Cyclophilins; D020104:Immunophilins