Uncoupling Protein

Ein Uncoupling Protein (‚Entkopplungsprotein‘) ist ein mitochondriales Membranprotein, das Protonen ohne chemiosmotische Kopplung durch die mitochondriale Membran lässt und somit die Atmungskette entkoppelt.[1]

Mitochondriales Uncoupling Protein 2

Eigenschaften

In Säugetieren gibt es fünf Typen:

UCP1 (synonym Thermogenin)[2]
UCP2[3]
UCP3[4]
SLC25A27 (synonym UCP4)[5]
SLC25A14 (synonym UCP5)[6]

Uncoupling Proteins dienen der Thermogenese, da die Protonen an Fettsäuren gebunden aus dem Inneren des Mitochondriums an der membranständigen ATPase vorbei ins Zytoplasma geschleust werden, um Neutralisationswärme zu erzeugen.[7] Chemische Entkoppler der Atmungskette sind z. B. 2,4-Dinitrophenol,[8] Carbonylcyanid m-chlorphenyl-Hydrazon (CCCP),[9] Malachitgrün,[10] Salicylsäure und teilweise auch Essigsäure. UCP werden durch Schilddrüsenhormone, Adrenalin, Noradrenalin und Leptin induziert.[11]

Weblinks

MeSH Uncoupling Protein

Einzelnachweise

Nedergaard J, Ricquier D, Kozak LP: Uncoupling proteins: current status and therapeutic prospects. In: EMBO Rep.. 6, Nr. 10, 2005, S. 917–21. doi:10.1038/sj.embor.7400532. PMID 16179945. PMC 1369193 (freier Volltext).
R. K. Porter: Uncoupling protein 1: a short-circuit in the chemiosmotic process. In: Journal of bioenergetics and biomembranes. Band 40, Nummer 5, Oktober 2008, S. 457–461, doi:10.1007/s10863-008-9172-8. PMID 18958609.
S. Diano, T. L. Horvath: Mitochondrial uncoupling protein 2 (UCP2) in glucose and lipid metabolism. In: Trends in Molecular Medicine. Band 18, Nummer 1, Januar 2012, S. 52–58, doi:10.1016/j.molmed.2011.08.003. PMID 21917523.
M. Nabben, J. Hoeks: Mitochondrial uncoupling protein 3 and its role in cardiac- and skeletal muscle metabolism. In: Physiology & behavior. Band 94, Nummer 2, Mai 2008, S. 259–269, doi:10.1016/j.physbeh.2007.11.039. PMID 18191161.
P. W. Ho, J. W. Ho, H. M. Tse, D. H. So, D. C. Yiu, H. F. Liu, K. H. Chan, M. H. Kung, D. B. Ramsden, S. L. Ho: Uncoupling protein-4 (UCP4) increases ATP supply by interacting with mitochondrial Complex II in neuroblastoma cells. In: PLOS ONE. Band 7, Nummer 2, 2012, S. e32810, doi:10.1371/journal.pone.0032810. PMID 22427795. PMC 3303587 (freier Volltext).
P. W. Ho, A. C. Chu, K. H. Kwok, M. H. Kung, D. B. Ramsden, S. L. Ho: Knockdown of uncoupling protein-5 in neuronal SH-SY5Y cells: Effects on MPP+-induced mitochondrial membrane depolarization, ATP deficiency, and oxidative cytotoxicity. In: Journal of neuroscience research. Band 84, Nummer 6, 2006, S. 1358–1366, doi:10.1002/jnr.21034. PMID 16941493.
P. Jezek, M. Jab?rek, K. D. Garlid: Channel character of uncoupling protein-mediated transport. In: FEBS letters. Band 584, Nummer 10, 2010, S. 2135–2141, doi:10.1016/j.febslet.2010.02.068. PMID 20206627. PMC 3617986 (freier Volltext).
Y. Jin, M. L. McEwen, S. A. Nottingham, W. F. Maragos, N. B. Dragicevic, P. G. Sullivan, J. E. Springer: The mitochondrial uncoupling agent 2,4-dinitrophenol improves mitochondrial function, attenuates oxidative damage, and increases white matter sparing in the contused spinal cord. In: Journal of neurotrauma. Band 21, Nummer 10, Oktober 2004, S. 1396–1404, PMID 15672630.
K. Kaila, K. Mattsson, J. Voipio: Fall in intracellular pH and increase in resting tension induced by a mitochondrial uncoupling agent in crayfish muscle. In: The Journal of physiology. Band 408, Januar 1989, S. 271–293, PMID 2778730. PMC 1190403 (freier Volltext).
G. Werth, A. Boiteux: Toxicity of triphenylmethane dyes. Malachite green as an uncoupling agent of oxidative phosphorylation in vivo and in vitro. In: Archiv für Toxikologie. Band 23, Nummer 2, 1968, S. 82–103, PMID 4299566.
Gong DW, He Y, Karas M, Reitman M: Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, β3-adrenergic agonists, and leptin. In: J Biol Chem. 272, Nr. 39, 1997, S. 24129–24132. doi:10.1074/jbc.272.39.24129.

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[pmid16179945-1] Nedergaard J, Ricquier D, Kozak LP: Uncoupling proteins: current status and therapeutic prospects. In: EMBO Rep.. 6, Nr. 10, 2005, S. 917–21. doi:10.1038/sj.embor.7400532. PMID 16179945. PMC 1369193 (freier Volltext).

[2] R. K. Porter: Uncoupling protein 1: a short-circuit in the chemiosmotic process. In: Journal of bioenergetics and biomembranes. Band 40, Nummer 5, Oktober 2008, S. 457–461, doi:10.1007/s10863-008-9172-8. PMID 18958609.

[3] S. Diano, T. L. Horvath: Mitochondrial uncoupling protein 2 (UCP2) in glucose and lipid metabolism. In: Trends in Molecular Medicine. Band 18, Nummer 1, Januar 2012, S. 52–58, doi:10.1016/j.molmed.2011.08.003. PMID 21917523.

[4] M. Nabben, J. Hoeks: Mitochondrial uncoupling protein 3 and its role in cardiac- and skeletal muscle metabolism. In: Physiology & behavior. Band 94, Nummer 2, Mai 2008, S. 259–269, doi:10.1016/j.physbeh.2007.11.039. PMID 18191161.

[5] P. W. Ho, J. W. Ho, H. M. Tse, D. H. So, D. C. Yiu, H. F. Liu, K. H. Chan, M. H. Kung, D. B. Ramsden, S. L. Ho: Uncoupling protein-4 (UCP4) increases ATP supply by interacting with mitochondrial Complex II in neuroblastoma cells. In: PLOS ONE. Band 7, Nummer 2, 2012, S. e32810, doi:10.1371/journal.pone.0032810. PMID 22427795. PMC 3303587 (freier Volltext).

[6] P. W. Ho, A. C. Chu, K. H. Kwok, M. H. Kung, D. B. Ramsden, S. L. Ho: Knockdown of uncoupling protein-5 in neuronal SH-SY5Y cells: Effects on MPP+-induced mitochondrial membrane depolarization, ATP deficiency, and oxidative cytotoxicity. In: Journal of neuroscience research. Band 84, Nummer 6, 2006, S. 1358–1366, doi:10.1002/jnr.21034. PMID 16941493.

[7] P. Jezek, M. Jab?rek, K. D. Garlid: Channel character of uncoupling protein-mediated transport. In: FEBS letters. Band 584, Nummer 10, 2010, S. 2135–2141, doi:10.1016/j.febslet.2010.02.068. PMID 20206627. PMC 3617986 (freier Volltext).

[8] Y. Jin, M. L. McEwen, S. A. Nottingham, W. F. Maragos, N. B. Dragicevic, P. G. Sullivan, J. E. Springer: The mitochondrial uncoupling agent 2,4-dinitrophenol improves mitochondrial function, attenuates oxidative damage, and increases white matter sparing in the contused spinal cord. In: Journal of neurotrauma. Band 21, Nummer 10, Oktober 2004, S. 1396–1404, PMID 15672630.

[9] K. Kaila, K. Mattsson, J. Voipio: Fall in intracellular pH and increase in resting tension induced by a mitochondrial uncoupling agent in crayfish muscle. In: The Journal of physiology. Band 408, Januar 1989, S. 271–293, PMID 2778730. PMC 1190403 (freier Volltext).

[10] G. Werth, A. Boiteux: Toxicity of triphenylmethane dyes. Malachite green as an uncoupling agent of oxidative phosphorylation in vivo and in vitro. In: Archiv für Toxikologie. Band 23, Nummer 2, 1968, S. 82–103, PMID 4299566.

[11] Gong DW, He Y, Karas M, Reitman M: Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, β3-adrenergic agonists, and leptin. In: J Biol Chem. 272, Nr. 39, 1997, S. 24129–24132. doi:10.1074/jbc.272.39.24129.