Xu X, Forbes J G, Colombini M
Department of Biology, University of Maryland, College Park, Maryland 20742, USA.
J Membr Biol. 2001 Mar 1;180(1):73-81. doi: 10.1007/s002320010060.
VDAC forms the major pathway for metabolites across the mitochondrial outer membrane. The regulation of the gating of VDAC channels is an effective way to control the flow of metabolites into and out of mitochondria. Here we present evidence that actin can modulate the gating process of Neurospora crassa VDAC reconstituted into membranes made with phosphatidylcholine. An actin concentration as low as 50 nM caused the VDAC-mediated membrane conductance to drop by as much as 85% at elevated membrane potentials. Actin's effect could be quickly reversed by adding pronase to digest the protein. alpha-Actin, from mammalian muscle, has a stronger effect than beta- and gamma-actin from human platelets. The monomeric form of actin, G-actin, is effective. Stabilization of the fibrous form, F-actin, with the mushroom toxin, phalloidin, blocks the effect of actin on VDAC, indicating that F-actin might be ineffective. Cytochalasin B did not interfere with the ability of actin to favor VDAC closure. DNase- did effectively block actin's effect on VDAC, and VDAC decreased actin's inhibitory effect on DNase-I activity, indicating that N. crassa VDAC competes with DNase-I for the same binding site on actin. The actin-VDAC interaction might be a mechanism by which actin regulates energy metabolism.
电压依赖性阴离子通道（VDAC）构成了代谢物穿过线粒体外膜的主要途径。调节VDAC通道的门控是控制代谢物进出线粒体流动的有效方式。在此我们提供证据表明，肌动蛋白可以调节重组到由磷脂酰胆碱制成的膜中的粗糙脉孢菌VDAC的门控过程。在膜电位升高时，低至50 nM的肌动蛋白浓度可使VDAC介导的膜电导下降多达85%。通过添加链霉蛋白酶消化该蛋白质，肌动蛋白的作用可迅速逆转。来自哺乳动物肌肉的α-肌动蛋白比来自人血小板的β-和γ-肌动蛋白具有更强的作用。肌动蛋白的单体形式，即G-肌动蛋白，是有效的。用蘑菇毒素鬼笔环肽稳定纤维状形式的F-肌动蛋白可阻断肌动蛋白对VDAC的作用，表明F-肌动蛋白可能无效。细胞松弛素B不会干扰肌动蛋白促进VDAC关闭的能力。脱氧核糖核酸酶I确实有效地阻断了肌动蛋白对VDAC的作用，并且VDAC降低了肌动蛋白对脱氧核糖核酸酶I活性的抑制作用，表明粗糙脉孢菌VDAC与脱氧核糖核酸酶I竞争肌动蛋白上的相同结合位点。肌动蛋白与VDAC的相互作用可能是肌动蛋白调节能量代谢的一种机制。
