Lamb Fred S, Moreland Jessica G, Miller Francis J
Department of Pediatrics, University of Iowa Hospitals and Clinics, University of Iowa Children's Hospital, and Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242, USA.
Antioxid Redox Signal. 2009 Jun;11(6):1335-47. doi: 10.1089/ars.2008.2448.
Endosome trafficking and function require acidification by the vacuolar ATPase (V-ATPase). Electrogenic proton (H+) transport reduces the pH and creates a net positive charge in the endosomal lumen. Concomitant chloride (Cl-) influx has been proposed to occur via ClC Cl-=H+ exchangers. This maintains charge balance and drives Cl- accumulation, which may itself be critical to endosome function. Production of reactive oxygen species (ROS) in response to cytokines occurs within specialized endosomes that form in response to receptor occupation. ROS production requires an NADPH oxidase (Nox) and the ClC-3 Cl-=H+ exchanger. Like the V-ATPase, Nox activity is highly electrogenic, but separates charge with an opposite polarity (lumen negative). Here we review established paradigms of early endosomal ion transport focusing on the relation between the V-ATPase and ClC proteins. Electrophysiologic constraints on Nox-mediated vesicular ROS production are then considered. The potential for ClC-3 to participate in charge neutralization of both proton (V-ATPase) and electron (Nox) transport is discussed. It is proposed that uncompensated charge separation generated by Nox enzymatic activity could be used to drive secondary transport into negatively charged vesicles. Further experimentation will be necessary to establish firmly the biochemistry and functional implications of endosomal ROS production.
内体运输和功能需要液泡型ATP酶（V-ATP酶）进行酸化。质子（H⁺）的电转运降低了pH值，并在内体腔中产生净正电荷。有人提出伴随的氯离子（Cl⁻）内流是通过ClC Cl⁻=H⁺交换体发生的。这维持了电荷平衡并驱动Cl⁻积累，而Cl⁻积累本身可能对内体功能至关重要。细胞因子刺激下活性氧（ROS）的产生发生在因受体被占据而形成的特殊内体中。ROS的产生需要NADPH氧化酶（Nox）和ClC-3 Cl⁻=H⁺交换体。与V-ATP酶一样，Nox活性具有高度的电致性，但电荷分离的极性相反（腔内为负）。在这里，我们回顾早期内体离子运输的既定模式，重点关注V-ATP酶与ClC蛋白之间的关系。然后考虑Nox介导的囊泡ROS产生的电生理限制。讨论了ClC-3参与质子（V-ATP酶）和电子（Nox）运输电荷中和的可能性。有人提出，Nox酶活性产生的未补偿电荷分离可用于驱动二级运输进入带负电荷的囊泡。需要进一步的实验来确定内体ROS产生的生物化学和功能意义。
