A Novel Member of Solute Carrier Family 25 (SLC25A42) Is a Transporter of Coenzyme A and Adenosine 3′,5′-Diphosphate in Human Mitochondria
A Novel Member of Solute Carrier Family 25 (SLC25A42) Is a Transporter of Coenzyme A and Adenosine 3′,5′-Diphosphate in Human Mitochondria
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DOI：
10.1074/jbc.m109.014118
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发表时间：
2009-07-03
影响因子：
4.8
通讯作者：
Palmieri, Ferdinando
中科院分区：
文献类型：
--
作者：
Fiermonte, Giuseppe;Paradies, Eleonora;Palmieri, Ferdinando
线粒体载体是跨线粒体内膜转运代谢物、核苷酸和辅因子从而连接胞质和基质功能的蛋白质家族。必需辅因子辅酶A（CoA）在线粒体基质外合成，因此必须转运到线粒体中，在那里它是许多基本过程所必需的。在这项工作中，我们已经在功能上鉴定和表征了SLC 25 A42，一种线粒体载体家族的新人类成员。SLC 25 A42基因（Haitina，T.，Lindblom，J.，Renstrom，T.，和Fredriksson，R.，2006，Genomics 88，779-790）在大肠杆菌中过表达，纯化并重构为磷脂囊泡。它的转运特性、动力学参数和对线粒体的靶向表明，SLC 25 A42蛋白是CoA和腺苷3 '，5'-二磷酸的线粒体转运蛋白。SLC 25 A42仅催化逆向交换转运，对CoA、脱磷酸CoA、ADP和腺苷3 '，5'-二磷酸表现出高转运亲和力，可饱和，并被米酵菌酸和其他线粒体载体抑制剂不同程度地抑制。SLC 25 A42的主要生理作用是将CoA输入线粒体以交换线粒体内（脱氧）腺嘌呤核苷酸和腺苷3 '，5'-二磷酸。这是第一次对辅酶A和腺苷3 '，5'-二磷酸的线粒体载体进行生物化学表征。
Mitochondrial carriers are a family of proteins that transport metabolites, nucleotides, and cofactors across the inner mitochondrial membrane thereby connecting cytosolic and matrix functions. The essential cofactor coenzyme A (CoA) is synthesized outside the mitochondrial matrix and therefore must be transported into mitochondria where it is required for a number of fundamental processes. In this work we have functionally identified and characterized SLC25A42, a novel human member of the mitochondrial carrier family. The SLC25A42 gene (Haitina, T., Lindblom, J., Renstrom, T., and Fredriksson, R., 2006, Genomics 88, 779-790) was overexpressed in Escherichia coli, purified, and reconstituted into phospholipid vesicles. Its transport properties, kinetic parameters, and targeting to mitochondria demonstrate that SLC25A42 protein is a mitochondrial transporter for CoA and adenosine 3',5'-diphosphate. SLC25A42 catalyzed only a counter-exchange transport, exhibited a high transport affinity for CoA, dephospho-CoA, ADP, and adenosine 3',5'-diphosphate, was saturable and inhibited by bongkrekic acid and other inhibitors of mitochondrial carriers to various degrees. The main physiological role of SLC25A42 is to import CoA into mitochondria in exchange for intramitochondrial (deoxy) adenine nucleotides and adenosine 3',5'-diphosphate. This is the first time that a mitochondrial carrier for CoA and adenosine 3',5'-diphosphate has been characterized biochemically.