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Difference between revisions of "Uncoupling proteins"

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{{MitoPedia
{{MitoPedia
|abbr=UCP
|abbr=UCP
|description='''Uncoupling proteins''' (UCPs) are mitochondrial anion carrier proteins that can be found in the inner mitochondrial membranes of animals and plants. UCP1 acts as an uncoupler by dissipating the electrochemical proton gradient ([[mitochondrial membrane potential]]), generated by the [[electron transfer system]] by pumping protons from the mitochondrial matrix to the mitochondrial intermembrane space.
|description='''Uncoupling proteins''' (UCPs) are mitochondrial anion carrier proteins that can be found in the inner mitochondrial membranes of animals and plants. [[Uncoupling protein 1 |UCP1]] acts as an uncoupler by dissipating the electrochemical proton gradient ([[mitochondrial membrane potential]]), generated by the [[electron transfer system]] by pumping protons from the mitochondrial matrix to the mitochondrial intermembrane space.
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{{MitoPedia topics
{{MitoPedia topics
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== Uncoupling protein homologues ==
== Uncoupling protein homologues ==


:::: The gene family of uncoupling proteins (UCP) includes five mitochondrial solute carriers 25 (SLC25), named UCP1 (SLC25A7), UCP2 (SLC25A48), UCP3 (SLC25A9), UCP4 (SLC25A27) and UCP5 (SLC25A14).<ref>Ramsden DB, Ho PW-L, Ho JW-M, Liu HF, So DHF, Tse HM, Chan KH, Ho SL (2012) Human neuronal uncoupling proteins 4 and 5 (UCP4 and UCP5): structural properties, regulation, and physiological role in protection against oxidative stress and mitochondrial dysfunction. Brain and Behavior 2:468–78.</ref>. These proteins have a tripartite structure and are located in the inner membrane of mitochondria. Presumably all of them contribute to the metabolic regulation elicited by cold exposure, including ROS and lipid metabolism, apoptosis and thermogenesis.<ref>Criscuolo F, Gonzalez‐Barroso MdM, Bouillaud F, Ricquier D, Miroux B, Sorci G (2005) Mitochondrial uncoupling proteins: New perspectives for evolutionary ecologists. Amer Naturalist 166:686-99.</ref> The thermogenic function of UCP1, which was the first uncoupling protein to be discovered in 1978 <ref>Nicholls DG, Bernson VSM, Heaton GM (1978) The identification of the component in the inner membrane of brown adipose tissue mitochondria responsible for regulating energy dissipation. In: Girardier L, Seydoux J, eds. Effectors of thermogenesis: Proceedings of a symposium held at geneva (switzerland) on 14 to 16 july 1977. Basel: BirkhĂ€user Basel. p89-93.</ref>, is already well established, whereas the exact functions of the closely related paralogues UCP2 and UCP3 are yet to be investigated. <ref>Cannon B, Nedergaard J (2004). Brown adipose tissue: Function and physiological significance. Physiol Rev 84:277-359.</ref> <ref>Ricquier D, Bouillaud F (2000) The uncoupling protein homologues: Ucp1, ucp2, ucp3, stucp and atucp. Biochem J 345:161-79.</ref>. UCP4 and UCP5 are primarily expressed in the central nervous system (CNS) where they function as essential uncouplers of oxidative phosphorylation, thereby exerting an important protective function for cells by reducing oxidative stress (ROS).
:::: The gene family of uncoupling proteins (UCP) includes five mitochondrial solute carriers 25 (SLC25), named [[Uncoupling protein 1 |UCP1]] (SLC25A7), [[Uncoupling protein 2 |UCP2]] (SLC25A48), UCP3 (SLC25A9), UCP4 (SLC25A27) and UCP5 (SLC25A14).<ref>Ramsden DB, Ho PW-L, Ho JW-M, Liu HF, So DHF, Tse HM, Chan KH, Ho SL (2012) Human neuronal uncoupling proteins 4 and 5 (UCP4 and UCP5): structural properties, regulation, and physiological role in protection against oxidative stress and mitochondrial dysfunction. Brain and Behavior 2:468–78.</ref>. These proteins have a tripartite structure and are located in the inner membrane of mitochondria. Presumably all of them contribute to the metabolic regulation elicited by cold exposure, including ROS and lipid metabolism, apoptosis and thermogenesis.<ref>Criscuolo F, Gonzalez‐Barroso MdM, Bouillaud F, Ricquier D, Miroux B, Sorci G (2005) Mitochondrial uncoupling proteins: New perspectives for evolutionary ecologists. Amer Naturalist 166:686-99.</ref>  
 
:::: The thermogenic function of UCP1, which was the first uncoupling protein to be discovered in 1978 <ref>Nicholls DG, Bernson VSM, Heaton GM (1978) The identification of the component in the inner membrane of brown adipose tissue mitochondria responsible for regulating energy dissipation. In: Girardier L, Seydoux J, eds. Effectors of thermogenesis: Proceedings of a symposium held at geneva (switzerland) on 14 to 16 july 1977. Basel: BirkhÀuser Basel. p89-93.</ref>, is already well established, whereas the exact functions of the closely related paralogues UCP2 and UCP3 are yet to be investigated. <ref>Cannon B, Nedergaard J (2004). Brown adipose tissue: Function and physiological significance. Physiol Rev 84:277-359.</ref> <ref>Ricquier D, Bouillaud F (2000) The uncoupling protein homologues: UCP1, UCP2, UCP3, STUCP and ATUCP. Biochem J 345:161-79.</ref>. UCP4 and UCP5 are primarily expressed in the central nervous system (CNS) where they function as essential uncouplers of oxidative phosphorylation, thereby exerting an important protective function for cells by reducing oxidative stress (ROS).
== Uncoupling protein 1 (UCP1) ==
 
:::: The uncoupling protein 1 (UCP1) is also called thermogenin and is predominantly found in brown adipose tissue (BAT). It is vital for the maintenance of body temperature, especially for small mammals. As the essential component of non-shivering thermogenesis, it possesses the ability to build and open a pore in the inner mitochondrial membrane through which protons may flow along their electrochemical gradient, generated by respiration, bypassing the ATP-producing re-entry site at the F1F0-ATP synthase. Thereby the energy stored in the electrochemical gradient is dissipated as heat.<ref>Rousset S, Alves-Guerra M-C, Mozo J, Miroux B, Cassard-Doulcier A-M, Bouillaud F, Ricquier D (2004) The biology of mitochondrial uncoupling proteins. Diabetes 53(Suppl 1):S130-35.</ref>
:::: UCP1 can be inhibited by cytosolic purine nucleotides in their di- and tri-phosphate form such as ADP, ATP, GDP and GTP. In the presence of Mg2+ cations, which can bind to the di- and tri-phosphate moieties of the purine nucleotides, this inhibitory effects is reduced.<ref>Klingenspor M, Fromme T (2012) Brown adipose tissue. In: Symonds ME, editor. Adipose tissue biology. Springer, New York. p39-69.</ref> The activation of UCP1 is induced by long-chain fatty acids, which are liberated as a result of adrenergic stimulation.<ref>Fedorenko A, Lishko PV, Kirichok Y (2012) Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria. Cell 151:400-13.</ref> Specifically, when norepinephrine is released by the sympathetic nervous system, it binds and stimulates the ÎČ3-adrenergic receptor of brown adipocytes, leading to the activation of adenylyl cyclase (AC) and an increase in the level of cAMP. The released messenger cAMP stimulates PKA, which phosphorylates and activates the lipases HSL as well as ATGL that subsequently degrade tri- and di-glycerides resulting in the release of free fatty acids. The long-chain, fatty acids get oxidized and activate UCP1, which thereby initiates the uncoupling of mitochondrial respiration from ATP synthesis by causing a proton leak. <ref>Cannon B, Nedergaard J (2004) Brown adipose tissue: Function and physiological significance. Physiol Rev 84:277-359.</ref> <ref>Klingenspor M (2003) Cold-induced recruitment of brown adipose tissue thermogenesis. Exp Physiol 88:141-48.</ref> However, the exact mode of action of UCP1 has not yet been completely understood.<ref>Bertholet AM, Kirichok Y (2016) UCP1: A transporter for H<sup>+</sup> and fatty acid anions. Biochimie 1-7.</ref> <ref>Li Y, Fromme T, Schweizer S, Schottl T, Klingenspor M (2014) Taking control over intracellular fatty acid levels is essential for the analysis of thermogenic function in cultured primary brown and brite/beige adipocytes. EMBO Reports 15:1069-76.</ref>
:::: During the first 30 years after the discovery of UCP1, it was believed that brown adipose tissue containing UCP1 can only be found in placental mammals, while it has since then been proven to be also present in marsupials, fish and amphibians.<ref>Hughes DA, Jastroch M, Stoneking M, Klingenspor M (2009) Molecular evolution of ucp1 and the evolutionary history of mammalian non-shivering thermogenesis. BMC Evol Biol 9:4.</ref> <ref>Klingenspor M, Fromme T, Hughes Jr DA, Manzke L, Polymeropoulos E, Riemann T, Trzcionka M, Hirschberg V, Jastroch M (2008) An ancient look at UCP1. Biochim Biophys Acta - Bioenergetics. 1777:637-41.</ref> Current research focuses on the question whether the different types of UCP1 share common characteristics and are evolutionary related. What has already been found out is that the murine as well as human UCP1 can be activated by fatty acids or retinoids and inhibited by purine nucleotides. However, there is also proof for interspecies differences, such as the discovery that rodent UCP1 orthologs exhibit a basal proton conductance, whereas human uncoupling proteins have selectively lost the basal proton conductance.<ref>RodrĂ­guez-SĂĄnchez L, Rial E (2016) The distinct bioenergetic properties of the human UCP1. Biochimie.</ref>


== References ==
== References ==

Revision as of 15:12, 4 June 2017


high-resolution terminology - matching measurements at high-resolution


Uncoupling proteins

Description

Uncoupling proteins (UCPs) are mitochondrial anion carrier proteins that can be found in the inner mitochondrial membranes of animals and plants. UCP1 acts as an uncoupler by dissipating the electrochemical proton gradient (mitochondrial membrane potential), generated by the electron transfer system by pumping protons from the mitochondrial matrix to the mitochondrial intermembrane space.

Abbreviation: UCP


MitoPedia topics: Uncoupler  

Communicated by Bufe A 2017-05-04.

Uncoupling protein homologues

The gene family of uncoupling proteins (UCP) includes five mitochondrial solute carriers 25 (SLC25), named UCP1 (SLC25A7), UCP2 (SLC25A48), UCP3 (SLC25A9), UCP4 (SLC25A27) and UCP5 (SLC25A14).[1]. These proteins have a tripartite structure and are located in the inner membrane of mitochondria. Presumably all of them contribute to the metabolic regulation elicited by cold exposure, including ROS and lipid metabolism, apoptosis and thermogenesis.[2]
The thermogenic function of UCP1, which was the first uncoupling protein to be discovered in 1978 [3], is already well established, whereas the exact functions of the closely related paralogues UCP2 and UCP3 are yet to be investigated. [4] [5]. UCP4 and UCP5 are primarily expressed in the central nervous system (CNS) where they function as essential uncouplers of oxidative phosphorylation, thereby exerting an important protective function for cells by reducing oxidative stress (ROS).

References

  1. ↑ Ramsden DB, Ho PW-L, Ho JW-M, Liu HF, So DHF, Tse HM, Chan KH, Ho SL (2012) Human neuronal uncoupling proteins 4 and 5 (UCP4 and UCP5): structural properties, regulation, and physiological role in protection against oxidative stress and mitochondrial dysfunction. Brain and Behavior 2:468–78.
  2. ↑ Criscuolo F, Gonzalez‐Barroso MdM, Bouillaud F, Ricquier D, Miroux B, Sorci G (2005) Mitochondrial uncoupling proteins: New perspectives for evolutionary ecologists. Amer Naturalist 166:686-99.
  3. ↑ Nicholls DG, Bernson VSM, Heaton GM (1978) The identification of the component in the inner membrane of brown adipose tissue mitochondria responsible for regulating energy dissipation. In: Girardier L, Seydoux J, eds. Effectors of thermogenesis: Proceedings of a symposium held at geneva (switzerland) on 14 to 16 july 1977. Basel: BirkhĂ€user Basel. p89-93.
  4. ↑ Cannon B, Nedergaard J (2004). Brown adipose tissue: Function and physiological significance. Physiol Rev 84:277-359.
  5. ↑ Ricquier D, Bouillaud F (2000) The uncoupling protein homologues: UCP1, UCP2, UCP3, STUCP and ATUCP. Biochem J 345:161-79.
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