Atractyloside binds

ATP-ADP translocase is specifically inhibited by very low concentrations of atractyloside (a plant glycoside) or bongkrekic acid (an antibiotic from a mold). Atractyloside binds to the translocase when its nucleotide site faces the cytosol, whereas bongkrekic acid binds when this site faces the mitochondrial matrix. Oxidative phosphorylation stops soon after either inhibitor is added, showing that ATP-ADP translocase is essential. 

Inhibitors of adenine nucleotide (ATP/ADP) translocation. Bongkrekic acid binds to the ATP binding site, whereas atractyloside binds to the ADP binding site of the translocator. 

Adenine nucleotide Atractyloside Binds to external conformation to preclude ADP... 

In the previous section we mentioned the ADP/ATP transporter, and it is also shown in Figure 17.2. This system allows the export of ATP and import of ADP. Because ATP and ADP have net charges of -4 and -3, respectively, at pH 7, the transport is not electroneutral and must occur at the expense of the membrane potential. Atractyloside and bongkrekic acid are inhibitors of this system, the former binding to the ADP binding site of the porter and the latter to the ATP site. Associated with ADP/ATP transport is the transport of P which must enter the mitochondrion to participate in ATP formation. Several systems for transport-... 

The essential role of cytochrome c release from injured mitochondria in the activation of caspase 9 has been alluded to above. This pathway is especially important in proapoptotic stimuli that are not initiated by surface receptors for apoptosis, such as UV irradiation, and may involve mitochondrial dependent pathways [83]. Continued respiration in the presence of an open mitochondrial pore may result in the generation of reactive oxygen species. Release of cytochrome c may be mediated by the opening of the mitochondrial FT pore, a non-selective channel whose composition is only partially defined [84]. Inhibitors of FT pore opening, such as cyclosporine, which binds to the adenine nucleotide translocator (ANT), a component of the FT pore, and bongkrekic acid, as well as Bcl-2, prevent cytochrome c release and inhibit apoptosis [85] whereas activators of the FT pore, such as atractyloside and Bax induce it [86]. Oxidants can rupture the outer membrane of mitochondria and release caspase-activating proteins [87]. Some studies have shown cytochrome c release before collapse of the mitochondrial membrane potential [83] suggesting alternate control of the FT pore. Many, but not all, of the members of the Bd-2 family of proteins reside in the inner mitochondrial membrane, form ionic channels in hpid membranes and increase rates of proton extrusion in mitochondria [88] and thus may control the FT pore. The antiapoptotic and mitochondrial affects of Bd-2 are independent of caspase activity as they occur in the presence of caspase inhibitors and also in yeast that lack caspases [86]. 

Atractyloside a glucoside from the Mediterranean thistle Atraclylis gummiiera. It is a competitive inhibitor of adenine nucleotide binding and transport across the inner mitochondrial membrane. The closely related carboxyatractylate binds with higher affinity (Kj 10 M) and is not displaced by adenine nucleotides. 

Atractyloside is a toxic glycoside from the rhizomes of the Mediterranean thistle Atractylis gummifera] it competes with ADP for binding to the carrier. 

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