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线粒体二羧酸载体在白色脂肪组织中的主要表达

Predominant expression of the mitochondrial dicarboxylate carrier in white adipose tissue.

作者信息

Das K, Lewis R Y, Combatsiaris T P, Lin Y, Shapiro L, Charron M J, Scherer P E

机构信息

Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.

出版信息

Biochem J. 1999 Dec 1;344 Pt 2(Pt 2):313-20.

Abstract

We report the identification of a novel mouse protein closely related to the family of mitochondrial uncoupling proteins and the oxoglutarate carrier. The cDNA encodes a protein of 287 amino acids that shares all the hallmark features of the mitochondrial transporter superfamily, including six predicted transmembrane domains. It is nearly identical to the sequence recently reported for the rat mitochondrial dicarboxylate carrier (DIC). We find that murine DIC (mDIC) is expressed at very high levels in mitochondria of white adipocytes and is strongly induced in the course of 3T3-L1 adipogenesis. To determine the consequences of the presence of mDIC on the mitochondrial membrane potential, we transiently expressed mDIC in 293-T cells. Overexpression of mDIC leads to significant mitochondrial hyperpolarization. In addition, exposure to cold down-regulates mDIC levels in vivo. In contrast, free fatty acids lead to an up-regulation of mDIC protein in 3T3-L1 adipocytes. This is the first report demonstrating preferential expression in white adipose tissue of any mitochondrial transporter. However, it remains to be determined which metabolic pathways most critically depend on high level expression of mDIC in the adipocyte.

摘要

我们报告了一种与线粒体解偶联蛋白家族和草酰戊二酸载体密切相关的新型小鼠蛋白的鉴定。该cDNA编码一个287个氨基酸的蛋白质,它具有线粒体转运蛋白超家族的所有标志性特征,包括六个预测的跨膜结构域。它与最近报道的大鼠线粒体二羧酸载体(DIC)序列几乎相同。我们发现小鼠DIC(mDIC)在白色脂肪细胞的线粒体中高水平表达,并在3T3-L1脂肪生成过程中被强烈诱导。为了确定mDIC的存在对线粒体膜电位的影响,我们在293-T细胞中瞬时表达mDIC。mDIC的过表达导致显著的线粒体超极化。此外,体内暴露于寒冷会下调mDIC水平。相反,游离脂肪酸会导致3T3-L1脂肪细胞中mDIC蛋白上调。这是首次报道任何线粒体转运蛋白在白色脂肪组织中的优先表达。然而,尚有待确定哪些代谢途径最关键地依赖于脂肪细胞中mDIC的高水平表达。

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