Caspase-1 activation of lipid metabolic pathways in response to bacterial pore-forming toxins promotes cell survival
Caspase-1 activation of lipid metabolic pathways in response to bacterial pore-forming toxins promotes cell survival
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DOI：
10.1016/j.cell.2006.07.033
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发表时间：
2006-09-22
期刊：
影响因子：
64.5
通讯作者：
van der Goot, F. Gisou
中科院分区：
文献类型：
--
作者：
Gurcel, Laure;Abrami, Laurence;van der Goot, F. Gisou
许多病原生物产生成孔毒素作为毒力因子。然而，靶细胞对这种膜损伤产生反应。在这里，我们表明，毒素诱导的膜透化导致细胞质钾的减少，这促进了一个多蛋白寡聚体先天免疫复合物，称为炎性小体的形成，和caspase-1的激活。此外，我们发现，在这种情况下，当呈现蛋白水解半胱天冬酶-1诱导激活膜生物发生的中央调节因子，甾醇调节元件结合蛋白（SREBP），这反过来又可能通过促进膜修复促进毒素攻击后的细胞存活。这项研究强调，除了其在通过处理白细胞介素的前体形式触发炎症中的既定作用外，胱天蛋白酶-1具有更广泛的作用，特别是将细胞内离子组成与脂质代谢途径、膜生物发生和存活联系起来。
Many pathogenic organisms produce pore-forming toxins as virulence factors. Target cells however mount a response to such membrane damage. Here we show that toxin-induced membrane permeabilization leads to a decrease in cytoplasmic potassium, which promotes the formation of a multiprotein oligomeric innate immune complex, called the inflammasome, and the activation of caspase-1. Further, we find that when rendered proteolytic in this context caspase-1 induces the activation of the central regulators of membrane biogenesis, the Sterol Regulatory Element Binding Proteins (SREBPs), which in turn promote cell survival upon toxin challenge possibly by facilitating membrane repair. This study highlights that, in addition to its well-established role in triggering inflammation via the processing of the precursor forms of interleukins, caspase-1 has a broader role, in particular linking the intracellular ion composition to lipid metabolic pathways, membrane biogenesis, and survival.