Electrophysiological Study of a Novel Large Pore Formed by Bax and the Voltage-dependent Anion Channel That Is Permeable to Cytochromec

摘要: The Bcl-2 family of proteins, consisting anti-apoptotic and pro-apoptotic members, regulates cell death by controlling mitochondrial membrane permeability that is crucial for apoptotic signal transduction. We have recently shown some these such as Bcl-xL, Bax, Bak, directly modulate the voltage-dependent anion channel (VDAC) thus regulate apoptogenic cytochrome crelease potential loss. To elucidate molecular mechanisms VDAC regulation an electrophysiological study was carried out. It found Bax created a large pore, with conductance levels 4- 10-fold greater than those channels, respectively. Although channels both show ion selectivity modulation their activity, VDAC-Bax had neither properties. Anti-apoptotic Bcl-xL its BH4 oligopeptide completely closed VDAC, in contrast to Bax. Cytochromec passed through single but not or planar lipid bilayer. These data provide direct evidence forms novel pore together