Counillon Laurent, Bouret Yann, Marchiq Ibtissam, Pouysségur Jacques
University of Nice-Sophia Antipolis, LP2M UMR7370, Faculty of Medicine, 28 Avenue Valombrose, 06107 Nice France; Laboratories of Excellence Ion Channel Science and Therapeutics, France.
University of Nice-Sophia Antipolis, LPMC UMR 7336, 28 Avenue Valrose, 06108 Nice, France.
Biochim Biophys Acta. 2016 Oct;1863(10):2465-80. doi: 10.1016/j.bbamcr.2016.02.018. Epub 2016 Mar 2.
The Na(+)/H(+)-exchanger NHE1 and the monocarboxylate transporters MCT1 and MCT4 are crucial for intracellular pH regulation, particularly under active metabolism. NHE1, a reversible antiporter, uses the energy provided by the Na(+) gradient to expel H(+) ions generated in the cytosol. The reversible H(+)/lactate(-) symporters MCT1 and 4 cotransport lactate and proton, leading to the net extrusion of lactic acid in glycolytic tumors. In the first two sections of this article we review important features and remaining questions on the structure, biochemical function and cellular roles of these transporters. We then use a fully-coupled mathematical model to simulate their relative contribution to pH regulation in response to lactate production, as it occurs in highly hypoxic and glycolytic tumor cells. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou.
钠氢交换体NHE1以及单羧酸转运体MCT1和MCT4对细胞内pH调节至关重要，尤其是在活跃代谢情况下。NHE1是一种可逆性反向转运体，利用钠离子梯度提供的能量排出胞质溶胶中产生的氢离子。可逆性氢/乳酸同向转运体MCT1和MCT4协同转运乳酸和质子，导致糖酵解肿瘤中乳酸的净排出。在本文的前两部分，我们综述了这些转运体在结构、生化功能和细胞作用方面的重要特征及尚存的问题。然后，我们使用一个完全耦合的数学模型来模拟它们在乳酸生成时对pH调节的相对贡献，就像在高度缺氧和糖酵解的肿瘤细胞中发生的那样。本文是由皮埃尔·松沃、皮埃尔·梅希勒和让 - 克洛德·马蒂诺编辑的名为《线粒体通道》的特刊的一部分。
