VDAC
Not an ion channel in the sense of a gateway for ions to change the transmembrane voltage or membrane potential, but rather the mitochondrial voltage-dependent anion channel (VDAC) controls the transit of adenine nucleotides, Ca2+, and other metabolites both into and out of the mitochondrion in a voltage dependent manner. It is constituent of the mitochondrial permeability transition pore (PTP). Three kinds of VDACs (1-3) are known to date[1].
The assumption has generally been that VDAC is constantly open during metabolism. Recent data, however, suggest that VDAC has the ability to close and inhibit exchange of metabolites within intact cells[2]. In the closed state, ions, but not small molecule metabolites, can penetrate VDAC pores; in the open state, both ions and metabolites pass through VDAC channels. In addition, the closed state is cation-selective, whereas the open state is anion-selective. VDACs are increasingly linked with the control of apoptosis[3],[4]. Since VDAC channels close early in the evolution of apoptosis with the consequence that mitochondria cannot release ATP or take up ADP, Pi and respiratory substrates from the cytosol, they induce mitochondrial dysfunction, release of oxidative species and, ultimately, non-apoptotic, oxidative cell death[5]. This process has a degree of selectivity for cells with activated RAS–RAF–MEK signaling.
[1] Ca2+-dependent control of the permeability properties of the mitochondrial outer membrane and voltage-dependent anion-selective channel (VDAC). Báthori G, Csordás G, Garcia-Perez C, Davies E, Hajnóczky G. J Biol Chem 2006, 281, 17347-17358.
[2] Voltage-dependent anion channel (VDAC) as mitochondrial governator—Thinking outside the box. J.J. Lemasters, E. Holmuhamedov. Biochim. Biophys. Act. 2006, 1762, 181 – 190.
[3] The voltage-dependent anion channel (VDAC): function in intracellular signaling, cell life and cell death. Shoshan-Barmatz V, Israelson A, Brdiczka D, Sheu SS. Curr Pharm Des 2006, 12, 2249-2270.
[4] The mitochondrial permeability transition pore may comprise VDAC molecules. I. Binary structure and voltage dependence of the pore. Szabó I, Zoratti M. FEBS Lett 1993, 330, 201-205.
[5] Mitochondrial outer membrane permeability change and hypersensitivity to digitonin early in staurosporine-induced apoptosis. S. Duan, P. Hajek, C. Lin, S.K. Shin, G. Attardi, A. Chomyn. J. Biol. Chem. 2003, 278, 1346 – 1353.