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The human uncoupling proteins 5 and 6 (UCP5/SLC25A14 and UCP6/SLC25A30) transport sulfur oxyanions, phosphate and dicarboxylates.
Biochimica et Biophysica Acta (BBA) - Bioenergetics ( IF 4.3 ) Pub Date : 2019-07-30 , DOI: 10.1016/j.bbabio.2019.07.010
Ruggiero Gorgoglione 1 , Vito Porcelli 1 , Antonella Santoro 1 , Lucia Daddabbo 1 , Angelo Vozza 2 , Magnus Monné 3 , Maria Antonietta Di Noia 1 , Luigi Palmieri 4 , Giuseppe Fiermonte 2 , Ferdinando Palmieri 4
Affiliation  

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 H2S degradation products) from the mitochondria, thereby modulating the level of the important signal molecule H2S.

中文翻译:

人解偶联蛋白5和6(UCP5 / SLC25A14和UCP6 / SLC25A30)运输硫氧阴离子,磷酸根和二羧酸根。

人类基因组编码溶质载体家族25(SLC25)的53个成员,也称为线粒体载体家族。在这项工作中,已经对该家族的两个成员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)进行了彻底的生化表征。它们在细菌中过表达,纯化并在磷脂囊泡中重构。它们的传输特性和动力学参数表明,UCP5和UCP6传输无机阴离子(硫酸根,亚硫酸根,硫代硫酸根和磷酸根),以及较小程度的各种二羧酸根(例如丙二酸根,苹果酸根和柠檬酸根),甚至更多地运输天冬氨酸和(仅UCP5)谷氨酸盐和三羧酸盐。两种载体都催化快速的反向交换运输和非常低的底物单向运输。运输是饱和的,并在不同程度上受到汞和其他线粒体载体抑制剂的抑制。硫酸盐和硫代硫酸盐的UCP5和UCP6的运输亲和力高于其他任何底物,而UCP5的比活性却远高于UCP6。有人提出,UCP5和UCP6的主要生理作用是催化线粒体的亚硫酸盐和硫代硫酸盐(H2S降解产物)的输出,从而调节重要信号分子H2S的水平。硫酸盐和硫代硫酸盐的UCP5和UCP6的运输亲和力高于其他任何底物,而UCP5的比活性却远高于UCP6。有人提出,UCP5和UCP6的主要生理作用是催化线粒体的亚硫酸盐和硫代硫酸盐(H2S降解产物)的输出,从而调节重要信号分子H2S的水平。硫酸盐和硫代硫酸盐的UCP5和UCP6的运输亲和力高于其他任何底物,而UCP5的比活性却远高于UCP6。有人提出,UCP5和UCP6的主要生理作用是催化线粒体的亚硫酸盐和硫代硫酸盐(H2S降解产物)的输出,从而调节重要信号分子H2S的水平。
更新日期:2019-11-01
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