Ruhr-Universität Bochum, Institut für Physiologische Chemie, Medizinische Fakultät, Gebäude MA3, D-44780 Bochum, Germany.
Cell Commun Signal. 2011 Nov 1;9:26. doi: 10.1186/1478-811X-9-26.
VacA, the vacuolating cytotoxin A of Helicobacter pylori, induces apoptosis in epithelial cells of the gastic mucosa and in leukocytes. VacA is released by the bacteria as a protein of 88 kDa. At the outer surface of host cells, it binds to the sphingomyelin of lipid rafts. At least partially, binding to the cells is facilitated by different receptor proteins. VacA is internalized by a clathrin-independent mechanism and initially accumulates in GPI-anchored proteins-enriched early endosomal compartments. Together with early endosomes, VacA is distributed inside the cells. Most of the VacA is eventually contained in the membranes of vacuoles. VacA assembles in hexameric oligomers forming an anion channel of low conductivity with a preference for chloride ions. In parallel, a significant fraction of VacA can be transferred from endosomes to mitochondria in a process involving direct endosome-mitochondria juxtaposition. Inside the mitochondria, VacA accumulates in the mitochondrial inner membrane, probably forming similar chloride channels as observed in the vacuoles. Import into mitochondria is mediated by the hydrophobic N-terminus of VacA. Apoptosis is triggered by loss of the mitochondrial membrane potential, recruitment of Bax and Bak, and release of cytochrome c.
空泡毒素 A（VacA）是幽门螺杆菌的一种空泡细胞毒素，可诱导胃黏膜上皮细胞和白细胞发生凋亡。VacA 作为一种 88kDa 的蛋白由细菌释放。在宿主细胞的外表面，它与鞘脂类的脂筏结合。至少部分结合是通过不同的受体蛋白来促进的。VacA 通过网格蛋白非依赖的机制被内化，并最初积累在富含 GPI 锚定蛋白的早期内体隔室中。VacA 与早期内体一起在细胞内分布。大多数 VacA 最终包含在液泡的膜中。VacA 组装成六聚体寡聚物，形成具有低电导率的阴离子通道，对氯离子有偏好。同时，VacA 的很大一部分可以通过涉及直接的内体-线粒体并列的过程从内体转移到线粒体。在线粒体中，VacA 在内膜中积累，可能在类似于在液泡中观察到的方式下形成类似的氯离子通道。线粒体的输入是由 VacA 的疏水性 N 端介导的。凋亡是通过线粒体膜电位的丧失、Bax 和 Bak 的募集以及细胞色素 c 的释放而触发的。
