Regulation of acid-base transporters by reactive oxygen species following mitochondrial fragmentation
Regulation of acid-base transporters by reactive oxygen species following mitochondrial fragmentation
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DOI：
10.1152/ajpcell.00411.2011
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发表时间：
2012-04-01
影响因子：
5.5
通讯作者：
Nehrke, Keith
中科院分区：
文献类型：
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作者：
Johnson, David;Allman, Erik;Nehrke, Keith
李建军，李建军。线粒体断裂后活性氧对酸碱转运蛋白的调控作用。[J] .中国生物医学工程学报，2016,32(2):444 - 444。首次发表于2012年1月11日；doi: 10.1152 / ajpcell.00411.2011。线粒体形态是由裂变和融合这两个对立过程之间的平衡决定的，每一个过程都由一组不同的蛋白质调节。线粒体动力学异常与多种疾病有关，包括神经退行性疾病，如阿尔茨海默病、帕金森病和显性视神经萎缩。虽然裂变和融合的遗传决定因素已经得到了很好的认识，但关于形态学改变导致这些疾病状态的潜在病理生理的机制尚不清楚。我们实验室之前的工作确定了线粒体动力学在哺乳动物细胞培养和遗传模式生物秀丽隐杆线虫细胞内pH稳态中的作用。在这里，我们展示了在失去线粒体内膜融合能力的突变动物中看到的酸化是通过活性氧（ROS）依赖机制发生的，并且可以通过使用专门针对线粒体基质的药理学抗氧化剂来抑制。研究大鼠肝脏克隆9细胞内源性哺乳动物酸碱转运蛋白活性的生理学方法支持ROS信号传导至钠质子交换器有助于酸化的观点。由于维持pH稳态对细胞功能和活力至关重要，这项工作的结果为线粒体内膜融合丧失的病理生理学提供了新的见解。
Johnson D, Allman E, Nehrke K. Regulation of acid-base transporters by reactive oxygen species following mitochondrial fragmentation. Am J Physiol Cell Physiol 302: C1045-C1054, 2012. First published January 11, 2012; doi:10.1152/ajpcell.00411.2011.-Mitochondrial morphology is determined by the balance between the opposing processes of fission and fusion, each of which is regulated by a distinct set of proteins. Abnormalities in mitochondrial dynamics have been associated with a variety of diseases, including neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, and dominant optic atrophy. Although the genetic determinants of fission and fusion are well recognized, less is known about the mechanism(s) whereby altered morphology contributes to the underlying pathophysiology of these disease states. Previous work from our laboratory identified a role for mitochondrial dynamics in intracellular pH homeostasis in both mammalian cell culture and in the genetic model organism Caenorhabditis elegans. Here we show that the acidification seen in mutant animals that have lost the ability to fuse their mitochondrial inner membrane occurs through a reactive oxygen species (ROS)-dependent mechanism and can be suppressed through the use of pharmacological antioxidants targeted specifically at the mitochondrial matrix. Physiological approaches examining the activity of endogenous mammalian acid-base transport proteins in rat liver Clone 9 cells support the idea that ROS signaling to sodium-proton exchangers contributes to acidification. Because maintaining pH homeostasis is essential for cell function and viability, the results of this work provide new insight into the pathophysiology associated with the loss of inner mitochondrial membrane fusion.