Predominant expression of the mitochondrial dicarboxylate carrier in white adipose tissue.
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.
Das
K
K
Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Lewis
R Y
RY
Combatsiaris
T P
TP
Lin
Y
Y
Shapiro
L
L
Charron
M J
MJ
Scherer
P E
PE
D016475:3T3 Cells; D000273:Adipose Tissue / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000502:physiology*; D002451:Cell Compartmentation; D002678:Chimera; D003080:Cold Temperature; D029382:Dicarboxylic Acid Transporters; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008928:Mitochondria / Q000502:physiology*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000096:biosynthesis; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014475:Uncoupling Agents
D002352:Carrier Proteins; D029382:Dicarboxylic Acid Transporters; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014475:Uncoupling Agents