SLC25A10
Identifiers
Aliases	SLC25A10, DIC, solute carrier family 25 member 10, MTDPS19
External IDs	OMIM: 606794; MGI: 1353497; HomoloGene: 6519; GeneCards: SLC25A10; OMA:SLC25A10 - orthologs
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q25.3 Start 81,712,236 bp[1] End 81,721,016 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 E2 Start 120,382,666 bp[2] End 120,390,013 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver mucosa of transverse colon right uterine tube human kidney duodenum mucosa of esophagus body of pancreas testicle left testis salivary gland Top expressed in right kidney yolk sac human kidney left lobe of liver subcutaneous adipose tissue proximal tubule epithelium of stomach duodenum lacrimal gland jejunum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function dicarboxylic acid transmembrane transporter activity protein binding sulfate transmembrane transporter activity thiosulfate transmembrane transporter activity oxaloacetate transmembrane transporter activity malate transmembrane transporter activity succinate transmembrane transporter activity antiporter activity transmembrane transporter activity Cellular component membrane mitochondrial membranes nucleus nucleoplasm mitochondrion mitochondrial inner membrane integral component of membrane Biological process gluconeogenesis dicarboxylic acid transport sulfide oxidation, using sulfide:quinone oxidoreductase ion transport mitochondrial transport sulfate transport thiosulfate transport oxaloacetate transport phosphate ion transmembrane transport succinate transmembrane transport malate transmembrane transport oxaloacetate(2-) transmembrane transport sulfate transmembrane transport transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1468 27376 Ensembl ENSG00000183048 ENSMUSG00000025792 UniProt Q9UBX3 Q9QZD8 RefSeq (mRNA) NM_001270888 NM_001270953 NM_012140 NM_013770 RefSeq (protein) NP_001257817 NP_001257882 NP_036272 NP_038798 Location (UCSC) Chr 17: 81.71 – 81.72 Mb Chr 11: 120.38 – 120.39 Mb PubMed search [3] [4]
Wikidata
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The mitochondrial dicarboxylate carrier (DIC) is an integral membrane protein encoded by the SLC25A10 gene in humans that catalyzes the transport of dicarboxylates such as malonate, malate, and succinate across the inner mitochondrial membrane in exchange for phosphate, sulfate, and thiosulfate by a simultaneous antiport mechanism, thus supplying substrates for the Krebs cycle, gluconeogenesis, urea synthesis, fatty acid synthesis, and sulfur metabolism.^{[5][6][7][8][9]}

The SLC25A10 gene is located on the q arm of chromosome 17 in position 25.3 and spans 8,781 base pairs.^[8] The gene has 11 exons and produces a 31.3 kDa protein composed of 287 amino acids.^[10][11] Intron 1 of this gene has five short Alu sequences.^[12][13] Mitochondrial dicarboxylate carriers are dimers, each consisting of six transmembrane domains with both the N- and C- terminus exposed to the cytoplasm.^[14] Like all mitochondrial carriers, dicarboxylate carriers features a tripartite structure with three repeats of about 100 amino acid residues, each of which contains a conserved sequence motif.^[15] These three tandem sequences fold into two anti-parallel transmembrane α-helices linked by hydrophilic sequences.^[6]

A crucial function of dicarboxylate carriers is to export malate from the mitochondria in exchange for inorganic phosphate. Dicarboxylate carriers are highly abundant in the adipose tissue and play a central role in supplying cytosolic malate for the citrate transporter, which then exchanges cytosolic malate for mitochondrial citrate to begin fatty acid synthesis.^[16] Abundant levels of DIC are also detected in the kidneys and liver, whereas lower levels are found in the lung, spleen, heart, and brain.^[12] Dicarboxylate carriers are involved in glucose-stimulated insulin secretion through pyruvate cycling, which mediates NADPH production, and by providing cytosolic malate as a counter-substrate for citrate export.^[17] It is also involved in reactive oxygen species (ROS) production through hyperpolarization of mitochondria and increases ROS levels when overexpressed.^[18] Furthermore, dicarboxylate carriers are crucial for cellular respiration, and inhibition of DIC impairs complex I activity in mitochondria.^[19]

Insulin causes a dramatic (approximately 80%) reduction of DIC expression in mice, whereas free fatty acids induces DIC expression. Cold exposure, which increases energy expenditure and decreases fatty acid biosynthesis, resulted in a significant (approximately 50%) reduction of DIC expression.^[14] DIC is inhibited by some dicarboxylate analogues, such as butylmalonate, as well as bathophenanthroline and thiol reagents such as Mersalyl and p-hydroxymercuribenzoate.^[20][21][22] The activity of dicarboxylate carriers has also been found to be upregulated in plants in response to stress.^[23] The rate of malonate uptake is inhibited by 2-oxoglutarate and unaffected by citrate, whereas the rates of succinate and malate uptake are inhibited by both 2-oxoglutarate and citrate.

Suppression of SLC25A10 down-regulated fatty acid synthesis in mice, resulting in decreased lipid accumulation in adipocytes. Additionally, knockout of SLC25A10 inhibited insulin-stimulated lipogenesis in adipocytes. These findings presents a possible target for anti-obesity treatments.^[16][24] It is also upregulated in tumors, which is likely because it regulates energy metabolism and redox homeostasis, both of which are frequently altered in tumor cells. In non-small cell lung cancer (NSCLC) cells, inhibition of SLC25A10 was found to increase the sensitivity to traditional anticancer drugs, and thus may present a potential target for anti-cancer strategies.^[25] Furthermore, overexpression of dicarboxylate carriers in renal proximal tubular cells has been found to cause a reversion to a non-diabetic state and protect cells from oxidative injury. This finding supports the dicarboxylate carriers as a potential therapeutic target to correct underlying metabolic disturbances in diabetic nephropathy.^[26]

This protein has binary interactions with NOTCH2NL, KRTAP5-9, KRTAP4-2, KRTAP10-8, MDFI, and KRT40.^[27][28]

• Solute carrier family

This article incorporates text from the United States National Library of Medicine, which is in the public domain.