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 Biosciences, Biotechnologies and Biopharmaceutics, Laboratory of Biochemistry and Molecular Biology, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy; Center of Excellence in Comparative Genomics, University of Bari, via Orabona 4, 70125 Bari, Italy.
Biochim Biophys Acta Bioenerg. 2019 Sep 1;1860(9):724-733. doi: 10.1016/j.bbabio.2019.07.010. Epub 2019 Jul 26.
The human genome encodes 53 members of the solute carrier family 25 (SLC25), also called the mitochondrial carrier family. In this work, two members of this family, UCP5 (BMCP1, brain mitochondrial carrier protein 1 encoded by SLC25A14) and UCP6 (KMCP1, kidney mitochondrial carrier protein 1 encoded by SLC25A30) have been thoroughly characterized biochemically. They were overexpressed in bacteria, purified and reconstituted in phospholipid vesicles. Their transport properties and kinetic parameters demonstrate that UCP5 and UCP6 transport inorganic anions (sulfate, sulfite, thiosulfate and phosphate) and, to a lesser extent, a variety of dicarboxylates (e.g. malonate, malate and citramalate) and, even more so, aspartate and (only UCP5) glutamate and tricarboxylates. Both carriers catalyzed a fast counter-exchange transport and a very low uniport of substrates. Transport was saturable and inhibited by mercurials and other mitochondrial carrier inhibitors at various degrees. The transport affinities of UCP5 and UCP6 were higher for sulfate and thiosulfate than for any other substrate, whereas the specific activity of UCP5 was much higher than that of UCP6. It is proposed that a main physiological role of UCP5 and UCP6 is to catalyze the export of sulfite and thiosulfate (the HS degradation products) from the mitochondria, thereby modulating the level of the important signal molecule HS.
人类基因组编码了溶质载体家族 25（SLC25）的 53 个成员，也称为线粒体载体家族。在这项工作中，该家族的两个成员 UCP5（BMCP1，由 SLC25A14 编码的脑线粒体载体蛋白 1）和 UCP6（KMCP1，由 SLC25A30 编码的肾线粒体载体蛋白 1）已在生化上得到了彻底的表征。它们在细菌中过表达，纯化并在磷脂囊泡中重建。它们的转运特性和动力学参数表明，UCP5 和 UCP6 转运无机阴离子（硫酸盐、亚硫酸盐、连硫酸盐和磷酸盐），并且在较小程度上转运各种二羧酸（例如丙二酸、苹果酸和柠檬酸），甚至天冬氨酸和（仅 UCP5）谷氨酸和三羧酸。两种载体都催化快速的反交换转运和非常低的底物单向转运。转运是可饱和的，并且被汞剂和其他线粒体载体抑制剂以不同程度抑制。UCP5 和 UCP6 对硫酸盐和连硫酸盐的转运亲和力高于任何其他底物，而 UCP5 的比活度远高于 UCP6。据推测，UCP5 和 UCP6 的主要生理作用是催化亚硫酸盐和连硫酸盐（HS 降解产物）从线粒体中输出，从而调节重要信号分子 HS 的水平。
