Degradative organelles contain enzymes that function optimally at the acidic pH generated by the V-ATPase. The resulting transmembrane H+ gradient also energizes the secondary transport of several solutes, including Cl−. We report that Cl− influx, driven by the 2Cl−/H+ exchanger ClC-7, is necessary for the resolution of phagolysosomes formed by macrophages. Cl− transported via ClC-7 had been proposed to provide the counterions required for electrogenic H+ pumping. However, we found that deletion of ClC-7 had a negligible effect on phagosomal acidification. Instead, luminal Cl− was found to be required for activation of a wide range of phagosomal hydrolases including proteases, nucleases, and glycosidases. These findings argue that the primary role of ClC-7 is the accumulation of (phago)lysosomal Cl− and that the V-ATPases not only optimize the activity of degradative hydrolases by lowering the pH but, importantly, also play an indirect role in their activation by providing the driving force for accumulation of luminal Cl− that stimulates hydrolase activity allosterically.

中文翻译：

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ClC-7 驱动吞噬体内氯化物积累，以支持水解酶活性和吞噬体分辨率

降解细胞器含有在 V-ATP 酶产生的酸性 pH 条件下发挥最佳功能的酶。由此产生的跨膜 H+ 梯度也会激发多种溶质的二次转运，包括 Cl−。我们报道，由 2Cl−/H+ 交换器 ClC-7 驱动的 Cl− 流入对于巨噬细胞形成的吞噬溶酶体的分解是必要的。已提出通过 ClC-7 传输 Cl− 来提供电 H+ 泵送所需的抗衡离子。然而，我们发现 ClC-7 的缺失对吞噬体酸化的影响可以忽略不计。相反，人们发现 Luminal Cl− 是激活多种吞噬体水解酶（包括蛋白酶、核酸酶和糖苷酶）所必需的。这些发现表明，ClC-7 的主要作用是（吞噬）溶酶体 Cl− 的积累，V-ATP 酶不仅通过降低 pH 值来优化降解水解酶的活性，而且重要的是，还在其降解过程中发挥间接作用。通过提供管腔 Cl− 积累的驱动力来变构刺激水解酶活性。