SLC25A31

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Solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 31
Identifiers
Symbols SLC25A31 ; AAC4; ANT4; SFEC35kDa
External IDs OMIM610796 MGI1920583 HomoloGene69485 GeneCards: SLC25A31 Gene
RNA expression pattern
PBB GE SLC25A31 221037 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 83447 73333
Ensembl ENSG00000151475 ENSMUSG00000069041
UniProt Q9H0C2 Q3V132
RefSeq (mRNA) NM_031291 NM_178386
RefSeq (protein) NP_112581 NP_848473
Location (UCSC) Chr 4:
127.73 – 127.77 Mb
Chr 3:
40.71 – 40.73 Mb
PubMed search [1] [2]

ADP/ATP translocase 4 (ANT4) is an enzyme that in humans is encoded by the SLC25A31 gene on chromosome 4.[1][2] This enzyme inhibits apoptosis by catalyzing ADP/ATP exchange across the mitochondrial membranes and regulating membrane potential.[2][3] In particular, ANT4 is essential to spermatogenesis, as it imports ATP into sperm mitochondria to support their development and survival.[3][4] Outside of this role, the SLC25AC31 gene has not been implicated in any human disease.[5][6]

Structure[edit]

The ANT4 protein contains six transmembrane helices, and a homodimer functional unit, which serves as an ADP/ATP channel protein.[5][7] Unlike the other three ANT isoforms, ANT4 has additional amino acids at its N- and C-terminals. These amino acid sequences may interact with different factors for specialized functions such as localization to sperm flagella.[3][4] The SLC25A31 gene is composed of 6 exons over a stretch of 44 kbp of DNA.[6]

Function[edit]

The ANT4 protein is a mitochondrial ADP/ATP carrier that catalyzes the exchange of ADP and ATP between the mitochondrial matrix and cytoplasm during ATP synthesis.[2] In addition, ANT4 stabilizes the mitochondrial membrane potential and decreases the permeability transition pore complex (PTPC) opening in order to prevent nuclear chromatin fragmentation and resulting cell death.[3] In humans, the protein localizes to the liver, brain and testis, though in adult males, it is expressed primarily in the testis.[3][5][6] Studies on Ant4-deficient mice reveal increased apoptosis in the testis leading to infertility, thus indicating that Ant4 is required as for spermatogenesis.[3] In this case, the anti-apoptotic function for ANT4 is attributed to its importing of cytosolic ATP into the mitochondria. In other cells, the isoform ANT2 carries out this role; however, since sperm lack the X chromosome on which the ANT2 gene resides, survival of the sperm is dependent on ANT4.[3][4]

Clinical Significance[edit]

To date, there is no evidence of SLC25A31 gene mutations associated with human disease, though they have been associated with male infertility in mice.[5][6] In addition, ANT4 overexpression has been observed to protect cancer cells from induced apoptosis by anti-cancer drugs such as lonidamine and staurosporine.[3]

Interactions[edit]

See also[edit]

References[edit]

  1. ^ Dolce V, Scarcia P, Iacopetta D, Palmieri F (Jan 2005). "A fourth ADP/ATP carrier isoform in man: identification, bacterial expression, functional characterization and tissue distribution". FEBS Lett 579 (3): 633–7. doi:10.1016/j.febslet.2004.12.034. PMID 15670820. 
  2. ^ a b c "Entrez Gene: SLC25A31 solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 31". 
  3. ^ a b c d e f g h Gallerne, C; Touat, Z; Chen, ZX; Martel, C; Mayola, E; Sharaf el dein, O; Buron, N; Le Bras, M; Jacotot, E; Borgne-Sanchez, A; Lemoine, A; Lemaire, C; Pervaiz, S; Brenner, C (May 2010). "The fourth isoform of the adenine nucleotide translocator inhibits mitochondrial apoptosis in cancer cells.". The international journal of biochemistry & cell biology 42 (5): 623–9. PMID 20060930. 
  4. ^ a b c Dupont, PY; Stepien, G (1 November 2011). "Computational analysis of the transcriptional regulation of the adenine nucleotide translocator isoform 4 gene and its role in spermatozoid glycolytic metabolism.". Gene 487 (1): 38–45. PMID 21827840. 
  5. ^ a b c d Hamazaki, T; Leung, WY; Cain, BD; Ostrov, DA; Thorsness, PE; Terada, N (21 April 2011). "Functional expression of human adenine nucleotide translocase 4 in Saccharomyces cerevisiae.". PloS one 6 (4): e19250. PMID 21532989. 
  6. ^ a b c d Clémençon, B; Babot, M; Trézéguet, V (2013). "The mitochondrial ADP/ATP carrier (SLC25 family): pathological implications of its dysfunction.". Molecular aspects of medicine 34 (2-3): 485–93. PMID 23506884. 
  7. ^ Chevrollier, A; Loiseau, D; Reynier, P; Stepien, G (June 2011). "Adenine nucleotide translocase 2 is a key mitochondrial protein in cancer metabolism.". Biochimica et biophysica acta 1807 (6): 562–7. PMID 20950584. 
  8. ^ Patten, DA; Wong, J; Khacho, M; Soubannier, V; Mailloux, RJ; Pilon-Larose, K; MacLaurin, JG; Park, DS; McBride, HM; Trinkle-Mulcahy, L; Harper, ME; Germain, M; Slack, RS (18 November 2014). "OPA1-dependent cristae modulation is essential for cellular adaptation to metabolic demand.". The EMBO journal 33 (22): 2676–91. PMID 25298396. 

Further reading[edit]

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