Mitochondrial uncoupling protein 4 explained

Mitochondrial uncoupling protein 4 is a protein that in humans is encoded by the SLC25A27 gene.^{[1] [2] [3]}

Mitochondrial uncoupling proteins (UCP) are members of the larger family of mitochondrial anion carrier proteins (MACP). UCPs separate oxidative phosphorylation from ATP synthesis with energy dissipated as heat, also referred to as the mitochondrial proton leak. UCPs facilitate the transfer of anions from the inner to the outer mitochondrial membrane and the return transfer of protons from the outer to the inner mitochondrial membrane. They also reduce the mitochondrial membrane potential in mammalian cells. Tissue specificity occurs for the different UCPs and the exact methods of how UCPs transfer H+/OH- are not known. UCPs contain the three homologous protein domains of MACPs. Transcripts of this gene are detected only in brain tissue and are specifically modulated by various environmental conditions.^[3] Recently, the proton transport activity of UCP4 has also been shown to be activated by fatty acids and inhibited by purine nucleotides.^[4] In addition, reconstituted UCP4 exhibited a distinct conformation, compared to other UCPs in the family.^[5]

See also

• Solute carrier family
• Uncoupling protein

Further reading

• Ricquier D, Bouillaud F . The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. . Biochem. J. . 345 . 2. 161–79 . 2000 . 10620491 . 10.1042/0264-6021:3450161 . 1220743 .
• Muzzin P . The uncoupling proteins. . Ann. Endocrinol. . 63 . 2 Pt 1 . 106–10 . 2002 . 11994670 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery. . Genome Res. . 6 . 9 . 791–806 . 1997 . 8889548 . 10.1101/gr.6.9.791 . free .
• Yu XX, Mao W, Zhong A, etal . Characterization of novel UCP5/BMCP1 isoforms and differential regulation of UCP4 and UCP5 expression through dietary or temperature manipulation. . FASEB J. . 14 . 11 . 1611–8 . 2000 . 10928996 . 10.1096/fj.14.11.1611 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Clark HF, Gurney AL, Abaya E, etal . The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. . Genome Res. . 13 . 10 . 2265–70 . 2003 . 12975309 . 10.1101/gr.1293003 . 403697 .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Liu D, Chan SL, de Souza-Pinto NC, etal . Mitochondrial UCP4 mediates an adaptive shift in energy metabolism and increases the resistance of neurons to metabolic and oxidative stress. . Neuromolecular Med. . 8 . 3 . 389–414 . 2007 . 16775390 . 10.1385/NMM:8:3:389 . 7377782 .
• Chan SL, Liu D, Kyriazis GA, etal . Mitochondrial uncoupling protein-4 regulates calcium homeostasis and sensitivity to store depletion-induced apoptosis in neural cells. . J. Biol. Chem. . 281 . 49 . 37391–403 . 2007 . 17035241 . 10.1074/jbc.M605552200 . free .
• Yasuno K, Ando S, Misumi S, etal . Synergistic association of mitochondrial uncoupling protein (UCP) genes with schizophrenia. . Am. J. Med. Genet. B Neuropsychiatr. Genet. . 144 . 2 . 250–3 . 2007 . 17066476 . 10.1002/ajmg.b.30443 . 30129988 .
• Ho PW, Ho JW, Tse HM, etal . Uncoupling protein-4 (UCP4) increases ATP supply by interacting with mitochondrial Complex II in neuroblastoma cells. . PLOS ONE . 7 . 2 . e32810 . 2012 . 22427795 . 10.1371/journal.pone.0032810 . 3303587. 2012PLoSO...732810H . free .
• Ho JW, Ho PW, Liu HF, etal . UCP4 is a target effector of the NF-κB c-Rel prosurvival pathway against oxidative stress. . Free Radic Biol Med . 53 . 2 . 383–394 . 2012 . 22580300 . 10.1016/j.freeradbiomed.2012.05.002 . free .

Notes and References

1. Mao W, Yu XX, Zhong A, Li W, Brush J, Sherwood SW, Adams SH, Pan G . UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells . FEBS Lett . 443 . 3 . 326–30 . Mar 1999 . 10025957 . 10.1016/S0014-5793(98)01713-X . 314036 .
2. Jezek P, Urbankova E . Specific sequence of motifs of mitochondrial uncoupling proteins . IUBMB Life . 49 . 1 . 63–70 . Jun 2000 . 10772343 . 10.1080/713803586 . 8541209 . free .
3. Web site: Entrez Gene: SLC25A27 solute carrier family 25, member 27.
4. Hoang T, Smith MD, Jelokhani-Niaraki M . Toward Understanding the Mechanism of Ion Transport Activity of Neuronal Uncoupling Proteins UCP2, UCP4, and UCP5 . Biochemistry . 51 . 19 . 4004–14 . 2012 . 22524567 . 10.1021/bi3003378.
5. Ivanova M, Hoang T, McSorly FR, Krnac G, Smith MD, Jelokhani-Niaraki M . A comparative study on conformation and ligand binding of the neuronal uncoupling proteins . Biochemistry . 49 . 3 . 512–21 . 2010 . 20000716 . 10.1021/bi901742g.