Fiermonte G, Palmieri L, Dolce V, Lasorsa F M, Palmieri F, Runswick M J, Walker J E
Department of Pharmaco-Biology, Laboratory of Biochemistry and Molecular Biology, University of Bari, Via Orabona 4, 70125 Bari, Italy.
J Biol Chem. 1998 Sep 18;273(38):24754-9. doi: 10.1074/jbc.273.38.24754.
The dicarboxylate carrier (DIC) belongs to a family of transport proteins found in the inner mitochondrial membranes. The biochemical properties of the mammalian protein have been characterized, but the protein is not abundant. It is difficult to purify and had not been sequenced. We have used the sequence of the distantly related yeast DIC to identify a related protein encoded in the genome of Caenorhabditis elegans. Then, related murine expressed sequence tags were identified with the worm sequence, and the murine sequence was used to isolate the cDNA for the rat homolog. The sequences of the worm and rat proteins have features characteristic of the family of mitochondrial transport proteins. Both proteins were expressed in bacteria and reconstituted into phospholipid vesicles where their transport characteristics closely resembled those of whole rat mitochondria and of the rat DIC reconstituted into vesicles. As expected from the role of the DIC in gluconeogenesis and ureogenesis, its transcripts were detected in rat liver and kidney, but unexpectedly, they were also detected in rat heart and brain tissues where the protein may fulfill other roles, possibly in supplying substrates to the Krebs cycle.
二羧酸载体（DIC）属于一类存在于线粒体内膜的转运蛋白家族。哺乳动物该蛋白的生化特性已得到表征，但该蛋白含量不高。它难以纯化且尚未测序。我们利用远缘相关的酵母DIC序列来鉴定秀丽隐杆线虫基因组中编码的一种相关蛋白。然后，用线虫序列鉴定出相关的小鼠表达序列标签，并利用小鼠序列分离大鼠同源物的cDNA。线虫和大鼠蛋白的序列具有线粒体转运蛋白家族的特征。两种蛋白均在细菌中表达并重组到磷脂囊泡中，其转运特性与完整大鼠线粒体以及重组到囊泡中的大鼠DIC的转运特性非常相似。正如DIC在糖异生和尿素生成中的作用所预期的那样，在大鼠肝脏和肾脏中检测到了它的转录本，但出乎意料的是，在大鼠心脏和脑组织中也检测到了，该蛋白可能在这些组织中发挥其他作用，可能是为三羧酸循环提供底物。
