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Two pathways for tBID‐induced cytochrome c release from rat brain mitochondria: BAK‐ versus BAX‐dependence
Author(s) -
Brustovetsky Nickolay,
Dubinsky Janet M.,
Antonsson Bruno,
Jemmerson Ronald
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01545.x
Subject(s) - mitochondrion , cytochrome c , voltage dependent anion channel , mitochondrial permeability transition pore , microbiology and biotechnology , cytosol , chemistry , apoptosis , biochemistry , biology , programmed cell death , bacterial outer membrane , enzyme , escherichia coli , gene
The mechanisms of truncated BID (tBID)‐induced Cyt c release from non‐synaptosomal brain mitochondria were examined. Addition of tBID to mitochondria induced partial Cyt c release which was inhibited by anti‐BAK antibodies, implicating BAK. Immunoblotting showed the presence of BAK, but not BAX, in brain mitochondria. tBID did not release Cyt c from rat liver mitochondria, which lacked both BAX and BAK. This indicated that tBID did not act independently of BAX and BAK. tBID plus monomeric BAX produced twice as much Cyt c release as did tBID or oligomeric BAX alone. Neither tBID alone nor in combination with BAX induced mitochondrial swelling. In both cases Cyt c release was insensitive to cyclosporin A plus ADP, inhibitors of the mitochondrial permeability transition (mPT). Recombinant Bcl‐xL inhibited Cyt c release induced by tBID alone or in combination with monomeric BAX. Koenig's polyanion, an inhibitor of VDAC, suppressed tBID‐induced Cyt c release from brain mitochondria mediated by BAK but not by BAX. Thus, tBID can induce mPT‐independent Cyt c release from brain mitochondria by interacting with exogenous BAX and/or with endogenous BAK that may involve VDAC. In contrast, neither adenylate kinase nor Smac/DIABLO was released from isolated rat brain mitochondria via BAK or BAX.