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Gene Review

SLC25A27  -  solute carrier family 25, member 27

Homo sapiens

Synonyms: FLJ33552, Mitochondrial uncoupling protein 4, Solute carrier family 25 member 27, UCP 4, UCP4, ...
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High impact information on SLC25A27


Biological context of SLC25A27


Anatomical context of SLC25A27

  • Consistent with its potential role as an uncoupling protein, UCP4 is localized to the mitochondria and its ectopic expression in mammalian cells reduces mitochondrial membrane potential [4].
  • PC12 neural cells expressing human UCP4 exhibit reduced Ca(2+) entry in response to thapsigargin-induced endoplasmic reticulum Ca(2+) store depletion [2].
  • However, the effect of UCP4 on adipocytes is unclear [6].
  • We previously showed that uncoupling protein 4 (UCP4) is differentially expressed in omental adipose tissue in diet-induced obese and normal rats [6].
  • In this work, we established a stable preadipocyte cell line overexpressing UCP4 to observe the direct effect of UCP4 on adipocytes [6].

Associations of SLC25A27 with chemical compounds


Other interactions of SLC25A27

  • This suggests that UCP4 represents the ancestral UCP from which other mammalian and plant UCPs diverged [3].
  • Protein sequence analyses showed that UCP4 is most related to UCP3 and possesses features characteristic of mitochondrial transporter proteins [4].
  • UCP2 and UCP4 expression were unaffected by UCP5 knockdown [8].
  • Phylogenetic analysis indicates that there are at least three clades of UCPs in invertebrates, which are closely related to vertebrate UCP1-3, UCP4, and UCP5, respectively, and shows early evolutionary divergence of UCPs, which pre-dates the divergence of protostomes and deuterostomes [9].
  • This study refutes the hypothesis of Hanak and Jezek (2001) that UCP4 is an ancestral form for all UCPs, and shows early evolutionary diversification of this protein family, which corresponds to their proposed functional diversity in regulation of proton leak, antioxidant defense and apoptosis [9].

Analytical, diagnostic and therapeutic context of SLC25A27

  • UCP4-mRNA expression is increased in neurons exposed to cold temperatures and in brain cells of rats maintained on caloric restriction, suggesting a role for UCP4 in the previously reported antiageing and neuroprotective effects of caloric restriction [7].


  1. Characterization of novel UCP5/BMCP1 isoforms and differential regulation of UCP4 and UCP5 expression through dietary or temperature manipulation. Yu, X.X., Mao, W., Zhong, A., Schow, P., Brush, J., Sherwood, S.W., Adams, S.H., Pan, G. FASEB J. (2000) [Pubmed]
  2. Mitochondrial Uncoupling Protein-4 Regulates Calcium Homeostasis and Sensitivity to Store Depletion-induced Apoptosis in Neural Cells. Chan, S.L., Liu, D., Kyriazis, G.A., Bagsiyao, P., Ouyang, X., Mattson, M.P. J. Biol. Chem. (2006) [Pubmed]
  3. Mitochondrial uncoupling proteins and phylogenesis--UCP4 as the ancestral uncoupling protein. Hanák, P., Jezek, P. FEBS Lett. (2001) [Pubmed]
  4. UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells. Mao, W., Yu, X.X., Zhong, A., Li, W., Brush, J., Sherwood, S.W., Adams, S.H., Pan, G. FEBS Lett. (1999) [Pubmed]
  5. Mitochondrial potassium channels and uncoupling proteins in synaptic plasticity and neuronal cell death. Mattson, M.P., Liu, D. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  6. Overexpression of uncoupling protein 4 promotes proliferation and inhibits apoptosis and differentiation of preadipocytes. Zhang, M., Wang, B., Ni, Y.H., Liu, F., Fei, L., Pan, X.Q., Guo, M., Chen, R.H., Guo, X.R. Life Sci. (2006) [Pubmed]
  7. Mitochondrial UCP4 mediates an adaptive shift in energy metabolism and increases the resistance of neurons to metabolic and oxidative stress. Liu, D., Chan, S.L., de Souza-Pinto, N.C., Slevin, J.R., Wersto, R.P., Zhan, M., Mustafa, K., de Cabo, R., Mattson, M.P. Neuromolecular Med. (2006) [Pubmed]
  8. Knockdown of uncoupling protein-5 in neuronal SH-SY5Y cells: Effects on MPP(+)-induced mitochondrial membrane depolarization, ATP deficiency, and oxidative cytotoxicity. Ho, P.W., Chu, A.C., Kwok, K.H., Kung, M.H., Ramsden, D.B., Ho, S.L. J. Neurosci. Res. (2006) [Pubmed]
  9. Evolution of mitochondrial uncoupling proteins: novel invertebrate UCP homologues suggest early evolutionary divergence of the UCP family. Sokolova, I.M., Sokolov, E.P. FEBS Lett. (2005) [Pubmed]
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