Mitochondrial voltage-dependent anion-selective channel

The Mitochondrial Voltage-Dependent Anion-Selective Channel... 

Figure 3. Schematic architecture of mitochondrial protein complexes. A transmembrane channel, called the permeability transition pore (FTP), is formed at the contaa sites between the inner and outer mitochondrial membrane (OM) of the mitochondria. The core components of PTP are the voltage-dependent anion channel (VDAC) in the outer membrane and the adenine nucleotide translocator (ANT) in the inner membrane (IM). VDAC allows diilusion of small molecules (<5 kDa), however ANT is only permeable to a few selected ions and metabolites and is responsible for maintaining the proton concentration gradient (pH) and the membrane elearic potential (A P,J. PTP is sometimes connected to destruction of permeability barrier and loss of the inner membrane potential and eventually results in mitochondrial membrane permeability transition during apoptosis and other specialized forms of cell death. Bax, Bak, Bc1-Xl and Bcl-2 locate in the outer membrane and may regulate the outer membrane permeability. The translocase of the outer membrane (TOM) and the translocase of the inner membrane (TlM) mediate protein import pathway in the mitochondria. Cy-D, cyclophilin D PBR, peripheral benzodiazepine receptor HK, hexokinase mtHSP70, mitochondrial heat shock protein 70.

By definition, the uncoupling effect of certain flavonoids should be independent of their inhibitory effects on mitochondrial respiration or FoFi-ATPase, suggesting an additional mode of action of flavonoids against mitochondrial function. A collapse of the transmembrane potential is likely under conditions in which the permeability barrier created by the mitochondrial inner membrane is compromised (as occurs in the presence of ionophores). Calcium, phosphate, oxidative stress, adenine nucleotide depletion, and membrane depolarization can induce such a nonspecific increase in the permeability of the inner membrane, in an event called the mitochondrial permeability transition (MPT) [30,34]. The MPT can be selectively inhibited by cyclosporin A and is believed to involve the assembly of a multiprotein complex to form a nonspecific pore that spans the inner and outer mitochondrial membranes. The latter assembly is referred to as the permeability transition pore complex (PTPC) (Fig. 1). Its exact composition is unknown, but appears to comprise cyclophilin D, ANT, the voltage-dependent anion channel (porin), and a benzodiazepinebinding site [10,30,34]. 

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