Members of the SLC25 mitochondrial carrier family link cytosolic and mitochondrial metabolism and support cellular maintenance and growth by transporting compounds across the mitochondrial inner membrane. Their monomeric or dimeric state and kinetic mechanism have been a matter of long-standing debate. It is believed by some that they exist as homodimers and transport substrates with a sequential kinetic mechanism, forming a ternary complex where both exchanged substrates are bound simultaneously. Some studies, in contrast, have provided evidence indicating that the mitochondrial ADP/ATP carrier (SLC25A4) functions as a monomer, has a single substrate binding site, and operates with a ping-pong kinetic mechanism, whereby ADP is imported before ATP is exported. Here we reanalyze the oligomeric state and kinetic properties of the human mitochondrial citrate carrier (SLC25A1), dicarboxylate carrier (SLC25A10), oxoglutarate carrier (SLC25A11), and aspartate/glutamate carrier (SLC25A13), all previously reported to be dimers with a sequential kinetic mechanism. We demonstrate that they are monomers, except for dimeric SLC25A13, and operate with a ping-pong kinetic mechanism in which the substrate import and export steps occur consecutively. These observations are consistent with a common transport mechanism, based on a functional monomer, in which a single central substrate-binding site is alternately accessible.

中文翻译：

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SLC25 家族的人类线粒体载体作为单体以乒乓动力学机制交换底物。


SLC25 线粒体载体家族的成员将细胞质和线粒体代谢联系起来，并通过跨线粒体内膜运输化合物来支持细胞的维持和生长。它们的单体或二聚体状态和动力学机制一直是一个长期争论的问题。一些人认为它们以同二聚体的形式存在，并以连续的动力学机制传输底物，形成三元复合物，其中两个交换的底物同时结合。相反，一些研究提供的证据表明线粒体 ADP/ATP 载体 (SLC25A4) 作为单体发挥作用，具有单一底物结合位点，并以乒乓动力学机制运行，即 ADP 在 ATP 输出之前输入。在这里，我们重新分析了人线粒体柠檬酸载体 (SLC25A1)、二羧酸载体 (SLC25A10)、氧化戊二酸载体 (SLC25A11) 和天冬氨酸/谷氨酸载体 (SLC25A13) 的寡聚状态和动力学特性，所有这些先前报道都是具有连续动力学的二聚体机制。我们证明，除了二聚体 SLC25A13 之外，它们都是单体，并以乒乓动力学机制运行，其中底物导入和导出步骤连续发生。这些观察结果与基于功能单体的常见转运机制一致，其中单个中心底物结合位点是可交替访问的。