Mitochondrial uncoupling protein 4

{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox gene}} '''Mitochondrial uncoupling protein 4''' (UCP4) is a protein that in humans is encoded by the ''SLC25A27'' gene.<ref name="Mao_1999">{{cite journal | vauthors = Mao W, Yu XX, Zhong A, Li W, Brush J, Sherwood SW, Adams SH, Pan G | title = UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells | journal = FEBS Letters | volume = 443 | issue = 3 | pages = 326–330 | date = Mar 1999 | pmid = 10025957 | doi = 10.1016/S0014-5793(98)01713-X | bibcode = 1999FEBSL.443..326M | s2cid = 314036 }}</ref><ref name="Jezek_2000">{{cite journal | vauthors = Jezek P, Urbankova E | title = Specific sequence of motifs of mitochondrial uncoupling proteins | journal = IUBMB Life | volume = 49 | issue = 1 | pages = 63–70 | date = Jun 2000 | pmid = 10772343 | doi = 10.1080/713803586 | s2cid = 8541209 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SLC25A27 solute carrier family 25, member 27 | url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=9481 }}</ref>

==Tissue distribution== ''SLC25A27'' transcripts are detected exclusively in brain tissue.<ref name="entrez" /> Expression of UCP4 is developmentally regulated and influenced by environmental conditions. This brain-specific expression pattern distinguishes UCP4 from other uncoupling proteins, which are found in a wider range of tissues.

==Structure== UCP4 shares the typical structural features of the MACP family, including three homologous protein domains that span the inner mitochondrial membrane. However, reconstituted UCP4 has been observed to adopt a conformation distinct from other uncoupling proteins, suggesting potential functional or regulatory differences.<ref name="Ivanova_2010">{{cite journal | vauthors = Ivanova M, Hoang T, McSorly FR, Krnac G, Smith MD, Jelokhani-Niaraki M | title = A comparative study on conformation and ligand binding of the neuronal uncoupling proteins | journal = Biochemistry | volume = 49 | issue = 3 | pages = 512–521 | date = Jan 2010 | pmid = 20000716 | doi = 10.1021/bi901742g }}</ref>

==Function== Mitochondrial uncoupling proteins (UCPs) are part of the mitochondrial anion carrier protein (MACP) family. They mediate proton leak across the inner mitochondrial membrane, uncoupling oxidative phosphorylation from ATP synthesis and dissipating energy as heat. This process lowers the mitochondrial membrane potential and contributes to thermogenesis and regulation of reactive oxygen species. UCPs facilitate the transport of anions from the mitochondrial matrix to the intermembrane space, and the reverse flow of protons. Their activity is modulated by various ligands; for example, UCP4 is activated by fatty acids and inhibited by purine nucleotides.<ref name="Hoang_2012">{{cite journal | vauthors = Hoang T, Smith MD, Jelokhani-Niaraki M | title = Toward Understanding the Mechanism of Ion Transport Activity of Neuronal Uncoupling Proteins UCP2, UCP4, and UCP5 | journal = Biochemistry | volume = 51 | issue = 19 | pages = 4004–4014 | date = May 2012 | pmid = 22524567 | doi = 10.1021/bi3003378 }}</ref>

==Homologs in ''Drosophila''== In ''Drosophila melanogaster'', four UCP homologs—DmUCP4A, DmUCP4B, DmUCP4C, and DmUCP5—have been identified based on sequence similarity to mammalian UCP4 and UCP5. Among these, DmUCP4A has been shown to protect against mitochondrial dysfunction in models of Parkinson's disease by increasing mitochondrial membrane potential and enhancing ATP synthesis. DmUCP4A functions as an aspartate transporter, catalyzing the unidirectional movement of aspartate from mitochondria to the cytosol. This transport is saturable, inhibited by mercurial compounds and other mitochondrial carrier inhibitors, and is not coupled to proton exchange. In ''Drosophila'', cytosolic aspartate is essential for protein and nucleotide biosynthesis, as well as the production of β-alanine and N-acetylaspartate—metabolites important for neuronal function.<ref>{{Cite journal | vauthors = Lunetti P, Gorgoglione R, Curcio R, Marra F, Pignataro A, Vozza A, Riley CL, Capobianco L, Palmieri L, Dolce V, Fiermonte G | title = Drosophila melanogaster Uncoupling Protein-4A (UCP4A) Catalyzes a Unidirectional Transport of Aspartate | journal = International Journal of Molecular Sciences | volume = 23 | issue = 3 | page = 1020 | date = 2022-01-18 | pmid = 35162943 | pmc = 8834685 | doi = 10.3390/ijms23031020 | language = en | doi-access = free | issn = 1422-0067 }}</ref>

==See also== * Solute carrier family * Uncoupling protein

==References== {{reflist}}

==Further reading== {{refbegin | 2}} *{{cite journal | vauthors = Ricquier D, Bouillaud F | title = The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. | journal = The Biochemical Journal | volume = 345 Pt 2 | issue = Pt 2 | pages = 161–179 | date = Jan 2000 | pmid = 10620491 | pmc = 1220743 | doi = 10.1042/0264-6021:3450161 }} *{{cite journal | vauthors = Muzzin P | title = The uncoupling proteins. | journal = Annales d'Endocrinologie | volume = 63 | issue = 2 Pt 1 | pages = 106–110 | date = Apr 2002 | pmid = 11994670 }} *{{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery. | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = Sep 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 | doi-access = free }} *{{cite journal | vauthors = Yu XX, Mao W, Zhong A, Schow P, Brush J, Sherwood SW, Adams SH, Pan G | title = Characterization of novel UCP5/BMCP1 isoforms and differential regulation of UCP4 and UCP5 expression through dietary or temperature manipulation. | journal = FASEB Journal | volume = 14 | issue = 11 | pages = 1611–1618 | date = Aug 2000 | pmid = 10928996 | doi = 10.1096/fj.14.11.1611 | doi-access = free }} *{{cite journal | vauthors = Liu D, Chan SL, Souza-Pinto NC, Slevin JR, Wersto RP, Zhan M, Mustafa K, Cabo R, Mattson MP | title = Mitochondrial UCP4 mediates an adaptive shift in energy metabolism and increases the resistance of neurons to metabolic and oxidative stress. | journal = Neuromolecular Medicine | volume = 8 | issue = 3 | pages = 389–414 | year = 2007 | pmid = 16775390 | doi = 10.1385/NMM:8:3:389 | s2cid = 7377782 | url = https://zenodo.org/record/1236307 }} *{{cite journal | vauthors = Chan SL, Liu D, Kyriazis GA, Bagsiyao P, Ouyang X, Mattson MP | title = Mitochondrial uncoupling protein-4 regulates calcium homeostasis and sensitivity to store depletion-induced apoptosis in neural cells. | journal = Journal of Biological Chemistry | volume = 281 | issue = 49 | pages = 37391–37403 | date = Dec 2006 | pmid = 17035241 | doi = 10.1074/jbc.M605552200 | doi-access = free | url = https://stars.library.ucf.edu/cgi/viewcontent.cgi?article=7011&context=facultybib2000 }} *{{cite journal | vauthors = Yasuno K, Ando S, Misumi S, Makino S, Kulski JK, Muratake T, Kaneko N, Amagane H, Someya T, Inoko H, Suga H, Kanemoto K, Tamiya G | title = Synergistic association of mitochondrial uncoupling protein (UCP) genes with schizophrenia. | journal = American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics | volume = 144B | issue = 2 | pages = 250–253 | date = Mar 2007 | pmid = 17066476 | doi = 10.1002/ajmg.b.30443 | s2cid = 30129988 }} *{{cite journal | vauthors = Ho PW, Ho JW, Tse HM, So DH, Yiu DC, Liu HF, Chan KH, Kung MH, Ramsden DB, Ho SL | title = Uncoupling protein-4 (UCP4) increases ATP supply by interacting with mitochondrial Complex II in neuroblastoma cells. | journal = PLOS ONE | volume = 7 | issue = 2 | article-number = e32810 | year = 2012 | pmid = 22427795 | pmc = 3303587 | doi = 10.1371/journal.pone.0032810 | bibcode = 2012PLoSO...732810H | doi-access = free }} *{{cite journal | vauthors = Ho JW, Ho PW, Liu HF, So DH, Chan KH, Tse ZH, Kung MH, Ramsden DB, Ho SL | title = UCP4 is a target effector of the NF-κB c-Rel prosurvival pathway against oxidative stress. | journal = Free Radical Biology & Medicine | volume = 53 | issue = 2 | pages = 383–394 | date = Jul 2012 | pmid = 22580300 | doi = 10.1016/j.freeradbiomed.2012.05.002 | doi-access = free }} {{refend}}

Category:Solute carrier family