Disease relevance of SLC25A6

• Influenza virus PB1-F2 protein induces cell death through mitochondrial ANT3 and VDAC1 [1].

High impact information on SLC25A6

• Interestingly, a homologue of ANT3, ANT2, maps to Xq and is subject to X-inactivation [2].
• This gene, ANT3, is located approximately 1,300 kilobases from the telomere, proximal to the pseudoautosomal gene CSF2RA, and escapes X-inactivation [2].
• Our results revealed that ANT1 and ANT3 over-expressing HeLa cells increased their atRA sensitivity [3].
• ANT3 is located in the pseudoautosomal region Xp22.3 and escapes X-inactivation [4].
• Moreover, the apoptosis produced by ANT3 was inhibited by bongkrekic acid and by cyclosporin A [5].

Biological context of SLC25A6

• Adenine nucleotide translocase 3 (ANT3) overexpression induces apoptosis in cultured cells [5].
• The three adenine nucleotide translocator (ANT1 to ANT3) isoforms, differentially expressed in human cells, play a crucial role in cell bioenergetics by catalyzing ADP and ATP exchange across the mitochondrial inner membrane [6].
• The ANT3 gene is transcribed from the centromere to the telomere and contains in its first intron a CpG island mapped 1300 kb from the telomere [7].
• The 3D positioning of ANT2 and ANT3 genes within female X chromosome territories correlates with gene activity [4].
• Three-color fluorescence in situ hybridization, confocal laser scanning microscopy, and three-dimensional image analysis revealed that transcriptionally active ANT2 and ANT3 genes were positioned more peripheral within their chromosome territory than the inactive ANT2 gene [4].

Anatomical context of SLC25A6

• Furthermore, regulation of ANT3 expression by IL-4 and IFN-gamma correlated with the modulation T cell survival by these cytokines from dex-induced apoptosis [8].
• The three-dimensional positioning of the X-chromosomal adenine nucleotide translocase genes, ANT2 and ANT3, were compared in the active and inactive X chromosome territories (Xa and Xi) of female human amniotic fluid cell nuclei [4].
• Binding to ANT-3 by the high affinity inhibitors BKA and ATR, as well as the lower affinity natural ligand ADP, was similar to that measured in bovine heart mitochondria, and to that previously reported for mammalian heart mitochondria [9].
• Human ANT-3 was cloned from a human heart cDNA library and expressed as a histidine-tagged fusion protein in the mitochondria of the Trichoplusia ni. cell line [9].

Other interactions of SLC25A6

• Transient overexpression of ANT3 resulted, like ANT1, in apoptosis as shown by an increase in the sub-G1 fraction, annexin V staining, low DeltaPsi(m), and activation of caspases 9 and 3 [5].
• The pro-apoptotic activities of the ANT1 and ANT3 isoforms contrast with the lack of apoptotic activity of ANT2 [5].
• Importantly, overexpression of ANT3 effectively protected T cells from dexamethasone-induced apoptosis, while forced expression of ANT1 caused apoptosis [10].

References