Description
Bongkrekic acid (11076-19-0) is a p potent inhibitory ligand of the mitochondrial adenine nucleotide translocase (ANT).1Inhibits mitochondrial permeability transition pore opening.2,3Delivery of bongkrekic acid to the mitochondria prevents apoptosis in HeLa cells.4
Uses
Bongkrekic acid solution has been used as an adenine nucleotide translocator (ANT) inhibitor to find out a different approach for the inhibition of oxidative phosphorylation in intact T98G cells. It has also been used as an inhibitor of the permeabilization transition pore complex (PTPC) pore and a tool to explore the role of PTPC in induction of apoptosis.
Definition
ChEBI: A tricarboxylic acid that is docosa-2,4,8,10,14,18,20-heptaenedioic acid substituted at positions 2 ,5 and 17 by methyl groups, at positions 6 by a methoxy group and at position 20 by a carboxymethyl group.
Biochem/physiol Actions
An antiapoptotic agent, it protects against NMDA receptor induced neuronal apoptosis,- extends cell survival in cells undergoing apoptosis following infection with viral vectors and abrogates apoptosis induced by hydrogen peroxide in T-cells. It is an inhibitor of adenine nucleotide translocase, which is a component of the mitochondrial permeability transition (MPT) pore complex. Bongkrekic acid prevents mitochondrial depolarization, swelling, rupture of mitochondrial outer membrane, and release of apoptogenic proteins such as cytochrome c. This phenomenon was observed during staurosporine induced apoptosis in Jurkat cells, in HepG2 undergoing apoptosis following TNF-α and ethanol.
Enzyme inhibitor
This toxic tricarboxylic acid (FWfree-acid = 486.61 g/mol; CAS 11076-19-0), produced Pseudomonas cocovenenans, is a potent competitive inhibitor of the mitochondrial ATP-ADP translocator, effectively blocking nucleotide binding to the carrier. The name is derived from bongkrek, a moldy coconut product produced in Indonesia. The toxin accumulates when P. cocovenenans outgrows the mold. Klingenberg et al. investigated bongkrekate binding to mitochondrial membrane to examine the reorienting site mechanism. The inferred mode of inhibition requires bongkrekate to bind to the single carrier site only from the inner face of the mitochondrial membrane (i.e., the matrix side)). They confirmed the pH-dependent accumulation of [3H]bongkrekate inside the mitochondria which superimposes onto the binding at carrier sites. By breaking the membrane with Lubrol or sonication, binding to the carrier sites could be titrated, and a Kd value of approximately 5 x 10–8 M was determined. The presence of ADP or ATP increases the amount of binding but does not alter the Kd. [35S]Atractylate is displaced by [3H]bongkrekate at a 1:1 molar ratio; this displacement is dependent on ADP concentration with the Km = 0.5 x 10–6 M. See also Atractyloside The isomer known as isobongkrekic acid, which has a cis-double bond at the dicarboxylic acid end of the molecule, has similar biological activity. Target(s): Adenine nucleotide translocator, ADP/ATP carrier; ATPase; bromelain, stem; papain; ficain, or ficin.
References
[1] M. ZIEGLER H P. The adenine nucleotide translocase modulates oligomycin-induced quenching of pyranine fluorescence in submitochondrial particles.[J]. The Journal of Biological Chemistry, 1993, 48 1: 25320-25328. DOI:
10.1016/s0021-9258(19)74394-4[2] P MARCHETTI. Mitochondrial permeability transition triggers lymphocyte apoptosis.[J]. Journal of immunology, 1996, 157 11: 4830-4836.
[3] NAOUFAL ZAMZAMI. Inhibitors of permeability transition interfere with the disruption of the mitochondrial transmembrane potential during apoptosis[J]. FEBS Letters, 1996, 384 1: 53-57. DOI:
10.1016/0014-5793(96)00280-3[4] YUMA YAMADA . Mitochondrial Delivery of Bongkrekic Acid Using a MITO-Porter Prevents the Induction of Apoptosis in Human HeLa Cells[J]. Journal of pharmaceutical sciences, 2013, 102 3: Pages 1008-1015. DOI:
10.1002/jps.23442
