Department of Biosciences, Biotechnologies and Biopharmaceutics, Laboratory of Biochemistry and Molecular Biology, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy.
Department of Sciences, University of Basilicata, Via Ateneo Lucano 10, 85100 Potenza, Italy.
Int J Mol Sci. 2019 Sep 10;20(18):4456. doi: 10.3390/ijms20184456.
Members of the mitochondrial carrier (MC) protein family transport various molecules across the mitochondrial inner membrane to interlink steps of metabolic pathways and biochemical processes that take place in different compartments; i.e., are localized partly inside and outside the mitochondrial matrix. MC substrates consist of metabolites, inorganic anions (such as phosphate and sulfate), nucleotides, cofactors and amino acids. These compounds have been identified by in vitro transport assays based on the uptake of radioactively labeled substrates into liposomes reconstituted with recombinant purified MCs. By using this approach, 18 human, plant and yeast MCs for amino acids have been characterized and shown to transport aspartate, glutamate, ornithine, arginine, lysine, histidine, citrulline and glycine with varying substrate specificities, kinetics, influences of the pH gradient, and capacities for the antiport and uniport mode of transport. Aside from providing amino acids for mitochondrial translation, the transport reactions catalyzed by these MCs are crucial in energy, nitrogen, nucleotide and amino acid metabolism. In this review we dissect the transport properties, phylogeny, regulation and expression levels in different tissues of MCs for amino acids, and summarize the main structural aspects known until now about MCs. The effects of their disease-causing mutations and manipulation of their expression levels in cells are also considered as clues for understanding their physiological functions.
线粒体载体（MC）蛋白家族的成员将各种分子转运穿过线粒体内膜，将代谢途径和生化过程的步骤连接起来，这些过程发生在不同的隔室中；也就是说，它们部分位于线粒体基质的内部和外部。MC 的底物包括代谢物、无机阴离子（如磷酸盐和硫酸盐）、核苷酸、辅因子和氨基酸。这些化合物是通过基于放射性标记底物摄取到用重组纯化的 MC 重建的脂质体的体外转运测定来鉴定的。通过使用这种方法，已经对 18 个人类、植物和酵母的氨基酸 MC 进行了表征，并显示出对天冬氨酸、谷氨酸、鸟氨酸、精氨酸、赖氨酸、组氨酸、瓜氨酸和甘氨酸的转运具有不同的底物特异性、动力学、pH 梯度的影响以及反向和单向转运模式的能力。除了为线粒体翻译提供氨基酸外，这些 MC 催化的转运反应在能量、氮、核苷酸和氨基酸代谢中至关重要。在这篇综述中，我们剖析了氨基酸 MC 的转运特性、系统发育、调节和在不同组织中的表达水平，并总结了迄今为止关于 MC 的主要结构方面。还考虑了它们致病突变的影响以及对其在细胞中表达水平的操纵，作为理解其生理功能的线索。
