Alternative titles; symbols
HGNC Approved Gene Symbol: SLC25A5
Cytogenetic location: Xq24 Genomic coordinates (GRCh38): X:119,468,444-119,471,396 (from NCBI)
ADP/ATP translocase, the most abundant mitochondrial protein, is an integral component of the inner mitochondrial membrane. It facilitates exchange of ADP and ATP between the cytosol and the mitochondria, thereby linking the subcellular compartment of ATP production to those of ATP utilization. SLC25A5 is 1 of at least 3 transcriptionally active ADP/ATP translocase genes in humans (Chen et al., 1990).
Battini et al. (1987) cloned an ADP/ATP translocase gene from an Okayama-Berg library derived from SV40-transformed human fibroblasts.
Ku et al. (1990) cloned and sequenced the ANT2 gene.
Chen et al. (1990) isolated 7 ADP/ATP translocase pseudogenes from recombinant human genomic libraries. Each pseudogene sequence had more than 85% identity with the sequence of the translocase cDNA derived from fibroblast mRNA, but each had mutations that precluded synthesis of a functional protein.
Mitochondrial nucleoids are large complexes containing, on average, 5 to 7 mitochondrial DNA (mtDNA) genomes and several proteins involved in mtDNA replication and transcription, as well as related processes. Bogenhagen et al. (2008) had previously shown that ANT2 was associated with native purified HeLa cell nucleoids. Using a formaldehyde crosslinking technique, they found that ANT2 copurified with mtDNA and was a core nucleoid protein.
Ito et al. (2010) showed that ANT2 coprecipitated with XPD (ERCC2; 126340), MIP18 (FAM96B; 614778), MMS19 (614777), and CIAO1 (604333) in a protein complex that was required for chromosome segregation in human cell lines.
Ku et al. (1990) determined that, like the other 2 ANT genes (103220, 300151), ANT2 has 4 exons. They identified differences in the sequence motif in the 5-prime-flanking regions of the 3 human translocase genes that could account for differences in the cell-type-specific and proliferation-associated expression.
Using an intron probe derived from a partial clone of the ANT2 gene, Chen et al. (1990) localized the gene to chromosome Xq13-q26. The assignment to the X chromosome and a particular region thereof was performed by analysis of somatic cell hybrids. By study of somatic cell hybrids containing different portions of the human X chromosome, Schiebel et al. (1994) narrowed the assignment to chromosome Xq24-q25. In connection with the previous assignment to Xq13-q26, the consensus location can be said to be Xq24-q26.
The mitochondrial permeability transition pore (mtPTP), a protein complex that includes the ANTs, mediates the sudden increase in inner mitochondrial membrane permeability that is a common feature of apoptosis. Kokoszka et al. (2004) confirmed that the mouse genome contains only 2 Ant genes, Ant1 and Ant2. They inactivated both Ant genes in mouse liver and analyzed mtPTP activation in isolated mitochondria and the induction of cell death in hepatocytes. Mitochondria lacking Ant could still undergo inner membrane permeability transition and release cytochrome c (123970). However, more Ca(2+) than usual was required to activate mtPTP, and the pore could not be regulated by Ant ligands, including adenine nucleotides. Hepatocytes without Ant remained competent to respond to various initiators of cell death. In addition, mutant mouse liver mitochondria showed respiration rates that were almost twice that of controls and that were unresponsive to the addition of ADP. The mitochondrial membrane potential was higher than that of controls. The increased respiration rate was associated with upregulated Cox1 (176805) protein levels.
Battini, R., Ferrari, S., Kaczmarek, L., Calabretta, B., Chen, S.-T., Baserga, R. Molecular cloning of a cDNA for a human ADP/ATP carrier which is growth-regulated. J. Biol. Chem. 262: 4355-4359, 1987. [PubMed: 3031073]
Bogenhagen, D. F., Rousseau, D., Burke, S. The layered structure of human mitochondrial DNA nucleoids. J. Biol. Chem. 283: 3665-3675, 2008. [PubMed: 18063578] [Full Text: https://doi.org/10.1074/jbc.M708444200]
Chen, S.-T., Chang, C.-D., Huebner, K., Ku, D.-H., McFarland, M., DeRiel, J. K., Baserga, R., Wurzel, J. A human ADP/ATP translocase gene has seven pseudogenes and localizes to chromosome X. Somat. Cell Molec. Genet. 16: 143-149, 1990. [PubMed: 2157297] [Full Text: https://doi.org/10.1007/BF01233044]
Ito, S., Tan, L. J., Andoh, D., Narita, T., Seki, M., Hirano, Y., Narita, K., Kuraoka, I., Hiraoka, Y., Tanaka, K. MMXD, a TFIIH-independent XPD-MMS19 protein complex involved in chromosome segregation. Molec. Cell 39: 632-640, 2010. [PubMed: 20797633] [Full Text: https://doi.org/10.1016/j.molcel.2010.07.029]
Kokoszka, J. E., Waymire, K. G., Levy, S. E., Sligh, J. E., Cai, J., Jones, D. P., MacGregor, G. R., Wallace, D. C. The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature 427: 461-465, 2004. [PubMed: 14749836] [Full Text: https://doi.org/10.1038/nature02229]
Ku, D.-H., Kagan, J., Chen, S.-T., Chang, C.-D., Baserga, R., Wurzel, J. The human fibroblast adenine nucleotide translocator gene: molecular cloning and sequence. J. Biol. Chem. 265: 16060-16063, 1990. [PubMed: 2168878]
Schiebel, K., Mertz, A., Winkelmann, M., Nagaraja, R., Rappold, G. Localization of the adenine nucleotide translocase gene ANT2 to chromosome Xq24-q25 with tight linkage to DXS425. Genomics 24: 605-606, 1994. [PubMed: 7713517] [Full Text: https://doi.org/10.1006/geno.1994.1675]