Uncoupling proteins are located in the inner mitochondria membrane. Their name is derived from their function: they uncouple oxidative procesess of the respiratory chain from ATP synthesis. Hitherto several members of the family have been described, the best known being UCP1. UCP1 can be expressed exclusively in brown adipose tissue and it is responsible for the heat production. In humans the brown fat disappears during the early childhood. In adults another members of the UCP family can be found--UCP2 and UCP3. It is widely accepted that these proteins affect lipid metabolism and energy expenditure. They are intensively studied owing to their possible use in the therapy of obesity. However, their physiological function has not been yet fully established.

• MeSH
• energetický metabolismus MeSH
• hnědá tuková tkáň fyziologie   MeSH
• iontové kanály MeSH
• lidé MeSH
• membránové proteiny fyziologie   MeSH
• membránové transportní proteiny * MeSH
• metabolismus lipidů MeSH
• mitochondriální proteiny * MeSH
• proteiny fyziologie   MeSH
• rozpřahující látky metabolismus   MeSH
• termoregulace MeSH
• transportní proteiny fyziologie   MeSH
• uncoupling protein 1 MeSH
• uncoupling protein 2 MeSH
• uncoupling protein 3 MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• iontové kanály MeSH
• membránové proteiny MeSH
• membránové transportní proteiny * MeSH
• mitochondriální proteiny * MeSH
• proteiny MeSH
• rozpřahující látky MeSH
• transportní proteiny MeSH
• UCP1 protein, human MeSH Prohlížeč
• UCP2 protein, human MeSH Prohlížeč
• UCP3 protein, human MeSH Prohlížeč
• uncoupling protein 1 MeSH
• uncoupling protein 2 MeSH
• uncoupling protein 3 MeSH

Brown adipose tissue (BAT) and brown in white (brite) adipose tissue, termed also beige adipose tissue, are major sites of mammalian nonshivering thermogenesis. Mitochondrial uncoupling protein 1 (UCP1), specific for these tissues, is the key factor for heat production. Recent molecular aspects of UCP1 structure provide support for the fatty acid cycling model of coupling, i.e. when UCP1 expels fatty acid anions in a uniport mode from the matrix, while uncoupling. Protonophoretic function is ensured by return of the protonated fatty acid to the matrix independent of UCP1. This mechanism is advantageous for mitochondrial uncoupling and compatible with heat production in a pro-thermogenic environment, such as BAT. It must still be verified whether posttranslational modification of UCP1, such as sulfenylation of Cys253, linked to redox activity, promotes UCP1 activity. BAT biogenesis and UCP1 expression, has also been linked to the pro-oxidant state of mitochondria, further endorsing a redox signalling link promoting an establishment of pro-thermogenic state. We discuss circumstances under which promotion of superoxide formation exceeds its attenuation by uncoupling in mitochondria and throughout point out areas of future research into UCP1 function.

• Klíčová slova
• Brown adipose tissue, Fatty acid cycling, Mitochondrial uncoupling protein1, Redox regulation, UCP1,
• MeSH
• hnědá tuková tkáň chemie   MeSH
• lidé MeSH
• mitochondriální proteiny metabolismus   MeSH
• oxidace-redukce MeSH
• posttranslační úpravy proteinů MeSH
• termogeneze * MeSH
• uncoupling protein 1 metabolismus   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• mitochondriální proteiny MeSH
• uncoupling protein 1 MeSH

Mitochondrial uncoupling proteins (UCPs) are pure anion uniporters, which mediate fatty acid (FA) uniport leading to FA cycling. Protonated FAs then flip-flop back across the lipid bilayer. An existence of pure proton channel in UCPs is excluded by the equivalent flux-voltage dependencies for uniport of FAs and halide anions, which are best described by the Eyring barrier variant with a single energy well in the middle of two peaks. Experiments with FAs unable to flip and alkylsulfonates also support this view. Phylogenetically, UCPs took advantage of the common FA-uncoupling function of SLC25 family carriers and dropped their solute transport function.

• MeSH
• biologické modely MeSH
• elektroforéza MeSH
• iontové kanály metabolismus   MeSH
• lidé MeSH
• mitochondriální proteiny metabolismus   MeSH
• protony MeSH
• uncoupling protein 1 MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• iontové kanály MeSH
• mitochondriální proteiny MeSH
• protony MeSH
• uncoupling protein 1 MeSH

We hypothesize that fatty acid-induced uncoupling serves in bioenergetic systems to set the optimum efficiency and tune the degree of coupling of oxidative phosphorylation. Uncoupling results from fatty acid cycling, enabled by several phylogenetically specialized proteins and, to a lesser extent, by other mitochondrial carriers. It is suggested that the regulated uncoupling in mammalian mitochondria is provided by uncoupling proteins UCP-1, UCP-2 and UCP-3, whereas in plant mitochondria by PUMP and StUCP, all belonging to the gene family of mitochondrial carriers. UCP-1, and hypothetically UCP-3, serve mostly to provide nonshivering thermogenesis in brown adipose tissue and skeletal muscle, respectively. Fatty acid cycling was documented for UCP-1, PUMP and ADP/ATP carrier, and is predicted also for UCP-2 and UCP-3. UCP-1 mediates a purine nucleotide-sensitive uniport of monovalent unipolar anions, including anionic fatty acids. The return of protonated fatty acid leads to H+ uniport and uncoupling. UCP-2 is probably involved in the regulation of body weight and energy balance, in fever, and defense against generation of reactive oxygen species. PUMP has been discovered in potato tubers and immunologically detected in fruits and corn, whereas StUCP has been cloned and sequenced froma a potato gene library. PUMP is supposed to act in the termination of synthetic processes in mature fruits and during the climacteric respiratory rise.

• MeSH
• biologické modely MeSH
• energetický metabolismus MeSH
• iontové kanály MeSH
• krysa rodu Rattus MeSH
• lidé MeSH
• mastné kyseliny metabolismus   MeSH
• membránové proteiny metabolismus   MeSH
• mitochondriální proteiny MeSH
• rozpřahující látky metabolismus   MeSH
• srdeční mitochondrie metabolismus   MeSH
• transportní proteiny metabolismus   MeSH
• uncoupling protein 1 MeSH
• uncoupling protein 3 MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• iontové kanály MeSH
• mastné kyseliny MeSH
• membránové proteiny MeSH
• mitochondriální proteiny MeSH
• rozpřahující látky MeSH
• transportní proteiny MeSH
• UCP1 protein, human MeSH Prohlížeč
• Ucp1 protein, rat MeSH Prohlížeč
• UCP3 protein, human MeSH Prohlížeč
• Ucp3 protein, rat MeSH Prohlížeč
• uncoupling protein 1 MeSH
• uncoupling protein 3 MeSH

The phenomena of fatty acid interaction with mitochondrial integral membrane proteins, namely uncoupling proteins (UCPs), are reviewed to emphasize the fatty acid cycling mechanism that has been suggested to explain the UCP function. Fatty acid-induced uncoupling is suggested to serve in bioenergetic systems, to set the optimum efficiency, and to tune the degree of coupling of oxidative phosphorylation. Fatty acid interaction with the "classic" uncoupling protein (UCP1) from mitochondria of thermogenic brown adipose tissue (BAT) is well known. UCP1 is considered to mediate purine nucleotide-sensitive uniport of monovalent unipolar anions, including anionic fatty acids. The return of protonated fatty acid leads to H+ uniport and uncoupling. Experiments supporting this mechanism are also reviewed for plant uncoupling mitochondrial protein (PUMP) and ADP/ATP carrier. The fatty acid cycling mechanism is predicted, as well for the recently discovered uncoupling proteins, UCP2 and UCP3.

• MeSH
• hnědá tuková tkáň metabolismus   MeSH
• iontové kanály MeSH
• lidé MeSH
• mastné kyseliny metabolismus   MeSH
• membránové proteiny metabolismus   MeSH
• mitochondriální proteiny MeSH
• mitochondrie metabolismus   MeSH
• předpověď MeSH
• proteolipidy metabolismus   MeSH
• rostliny MeSH
• rozpřahující látky metabolismus   MeSH
• transportní proteiny metabolismus   MeSH
• uncoupling protein 1 MeSH
• vazebná místa MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• iontové kanály MeSH
• mastné kyseliny MeSH
• membránové proteiny MeSH
• mitochondriální proteiny MeSH
• proteolipidy MeSH
• proteoliposomes MeSH Prohlížeč
• rozpřahující látky MeSH
• transportní proteiny MeSH
• UCP1 protein, human MeSH Prohlížeč
• uncoupling protein 1 MeSH

The mammalian uncoupling protein (UCP-1) from the gene family of mitochondrial carriers is a dimer of identical 33 kDa subunits, each containing six membrane-spanning alpha-helices. Its expression, restricted to brown fat, occurs upon birth, cold acclimation and overfeeding. UCP-1 dissipates redox energy and thereby provides heat to the animal. Two additional isoforms have recently been discovered, 59% homologous UCP-2, widely expressed (heart, kidney, lung, placenta, lymphocytes, white fat); and UCP-3 (57% homologous), found in brown fat and skeletal muscle. Their physiological roles are unknown, but may include the regulation of body weight and energy balance, muscle nonshivering thermogenesis, fever, and defense against generation of reactive oxygen species. Consequently, great pharmacological potential is expected in revealing their biochemical and hormonal regulators. UCP-1 mediates a purine-nucleotide-sensitive uniport of monovalent unipolar anions, including fatty acids, that lead to fatty acid cycling and uncoupling. UCP-2 and UCP-3 are expected to share a similar mechanism.

• MeSH
• biologický transport MeSH
• hnědá tuková tkáň metabolismus   MeSH
• iontové kanály MeSH
• lidé MeSH
• mastné kyseliny metabolismus   MeSH
• membránové proteiny chemie   genetika   metabolismus   MeSH
• mitochondriální proteiny MeSH
• molekulární sekvence - údaje MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin MeSH
• tkáňová distribuce MeSH
• transportní proteiny chemie   genetika   metabolismus   MeSH
• uncoupling protein 1 MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• iontové kanály MeSH
• mastné kyseliny MeSH
• membránové proteiny MeSH
• mitochondriální proteiny MeSH
• transportní proteiny MeSH
• UCP1 protein, human MeSH Prohlížeč
• uncoupling protein 1 MeSH

Instead of a comprehensive review, we describe the basic undisputed facts and a modest contribution of our group to the fascinating area of the research on mitochondrial uncoupling proteins. After defining the terms uncoupling, leak, protein-mediated uncoupling, we discuss the assumption that due to their low abundance the novel mitochondrial uncoupling proteins (UCP2 to UCP5) can provide only a mild uncoupling, i.e. can decrease the proton motive force by several mV only. Contrary to this, the highly thermogenic role of UCP1 in brown adipose tissue is not given only by its high content (approximately 5 % of mitochondrial proteins) but also by the low ATP synthase content and high capacity respiratory chain. Fatty acid cycling mechanism as a plausible explanation for the protonophoretic function of all UCPs and some other mitochondrial carriers is described together with the experiments supporting it. The phylogenesis of all UCPs, estimated UCP2 content in several tissues, and details of UCP2 activation are described on the basis of our experiments. Functional activation of UCP2 is proposed to decrease reactive oxygen species (ROS) production. Moreover, reaction products of lipoperoxidation such as cleaved hydroperoxy-fatty acids and hydroxy-fatty acid can activate UCP2 and promote feedback down-regulation of mitochondrial ROS production.

• MeSH
• down regulace MeSH
• iontové kanály MeSH
• lidé MeSH
• mastné kyseliny metabolismus   MeSH
• membránové proteiny metabolismus   MeSH
• mitochondriální proteiny MeSH
• mitochondrie metabolismus   MeSH
• mozek metabolismus   MeSH
• orgánová specificita MeSH
• protein - isoformy metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• svaly metabolismus   MeSH
• transportní proteiny metabolismus   MeSH
• uncoupling protein 1 MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• iontové kanály MeSH
• mastné kyseliny MeSH
• membránové proteiny MeSH
• mitochondriální proteiny MeSH
• protein - isoformy MeSH
• reaktivní formy kyslíku MeSH
• transportní proteiny MeSH
• UCP1 protein, human MeSH Prohlížeč
• uncoupling protein 1 MeSH

Metabolism of white adipose tissue is involved in the control of body fat content. In vitro experiments indicated a dependence of lipogenesis on mitochondrial ATP production, as well as a reciprocal link between hormonal effects on metabolism and energetics of adipocytes. Therefore, mitochondrial uncoupling in adipocytes that results in stimulation of energy dissipation and depression of ATP synthesis may contribute to control of lipid metabolism and adiposity. This is supported by the expression of protonophoric proteins in adipocytes, e.g. uncoupling proteins (UCPs) 2 and 5, and some anion transporters, and induction of UCP1 and UCP3 in white fat by pharmacological treatments that reduce adiposity. Negative correlation between expression of UCPs in adipocytes and accumulation of white fat was also found. Expression of UCP1 from the adipose-specific promoter in aP2-Ucp1 transgenic mice mitigated obesity induced by genetic or dietary factors. The obesity resistance, accompanied by mitochondrial uncoupling in adipocytes and increased energy expenditure, resulted from ectopic expression of UCP1 in white but not in brown fat. Probably due to depression of ATP/ADP ratio in white fat of transgenic mice, both fatty acid synthesis and lipolytic action of noradrenaline in adipocytes were relatively low. These results support the role of protonophoric proteins in adipocytes in the control of adiposity. The main function of these proteins in white fat may be modulation of lipogenesis and intracellular hormone signalling. Augmentation of energy expenditure may be of relatively small importance, in accordance with the low oxidative capacity of white adipocytes.

• MeSH
• biologické modely MeSH
• iontové kanály MeSH
• lidé MeSH
• membránové proteiny genetika   metabolismus   MeSH
• metabolismus lipidů * MeSH
• mitochondriální proteiny MeSH
• mitochondrie metabolismus   MeSH
• myši MeSH
• transportní proteiny genetika   metabolismus   MeSH
• tuková tkáň metabolismus   MeSH
• tukové buňky metabolismus   MeSH
• uncoupling protein 1 MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• iontové kanály MeSH
• membránové proteiny MeSH
• mitochondriální proteiny MeSH
• transportní proteiny MeSH
• UCP1 protein, human MeSH Prohlížeč
• Ucp1 protein, mouse MeSH Prohlížeč
• uncoupling protein 1 MeSH

Thermogenic uncoupling has been proven only for UCP1 in brown adipose tissue. All other isoforms of UCPs are potentially acting in suppression of mitochondrial reactive oxygen species (ROS) production. In this contribution we show that BAT mitochondria can be uncoupled by lauric acid in the range of approximately 100 nM when endogenous fatty acids are combusted by carnitine cycle and beta-oxidation is properly separated from the uncoupling effect. Respiration increased up to 3 times when related to the lowest fatty acid content (BSA present plus carnitine cycle). We also illustrated that any effect leading to more coupled states leads to enhanced H2O2 generation and any effect resulting in uncoupling gives reduced H2O2 generation in BAT mitochondria. Finally, we report doubling of plant UCP transcript in cells as well as amount of protein detected by 3H-GTP-binding sites in mitochondria of shoots and roots of maize seedlings subjected to the salt stress.

• MeSH
• buněčné dýchání MeSH
• guanosintrifosfát metabolismus   MeSH
• hnědá tuková tkáň metabolismus   MeSH
• iontové kanály MeSH
• karnitin metabolismus   MeSH
• kořeny rostlin metabolismus   MeSH
• kukuřice setá metabolismus   MeSH
• kyseliny laurové metabolismus   farmakologie   MeSH
• mastné kyseliny metabolismus   MeSH
• membránové proteiny fyziologie   MeSH
• mitochondriální proteiny MeSH
• mitochondrie metabolismus   MeSH
• oxidační stres MeSH
• peroxid vodíku metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• rostlinné proteiny fyziologie   MeSH
• rozpřahující látky metabolismus   farmakologie   MeSH
• savci MeSH
• techniky in vitro MeSH
• transportní proteiny fyziologie   MeSH
• uncoupling protein 1 MeSH
• vazebná místa MeSH
• výhonky rostlin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• guanosintrifosfát MeSH
• iontové kanály MeSH
• karnitin MeSH
• kyseliny laurové MeSH
• lauric acid MeSH Prohlížeč
• mastné kyseliny MeSH
• membránové proteiny MeSH
• mitochondriální proteiny MeSH
• peroxid vodíku MeSH
• reaktivní formy kyslíku MeSH
• rostlinné proteiny MeSH
• rozpřahující látky MeSH
• transportní proteiny MeSH
• uncoupling protein 1 MeSH

Uncoupling proteins (UCPs) belong to a distinct cluster of the mitochondrial anion carrier family. Up to five different uncoupling protein types were found in mitochondria of mammals and plants, and recently in fishes, fungi and protozoa. They exhibit a significantly conserved structure with several motifs specific to either the whole cluster or protein type. Uncoupling proteins, as well as the whole mitochondrial anion carrier gene family, probably emerged in evolution before the separation of animal, fungi, and plant kingdoms and originate from an anion/nucleotide or anion/anion transporter ancestor. Mammalian UCP1, UCP2, UCP3, and plant uncoupling proteins pUCP1 and pUCP2 are similar and seem to form one subgroup, whereas UCP4 and BMCP1 belong to a different group. Molecular, biochemical, and phylogenic data suggest that UCP2 could be considered as an UCP-prototype. UCP1 plays its biological role mainly in the non-shivering thermogenesis while the role of the other types is unknown. However, hypotheses have suggested that they are involved in the general balance of basic energy expenditure, protection from reactive oxygen species, and, in plants, in fruit ripening and seed ontogeny.

• MeSH
• fylogeneze MeSH
• fyziologie rostlin MeSH
• iontové kanály MeSH
• membránové proteiny chemie   klasifikace   genetika   metabolismus   MeSH
• mitochondriální proteiny MeSH
• mitochondrie metabolismus   MeSH
• molekulární sekvence - údaje MeSH
• rostlinné proteiny chemie   klasifikace   genetika   metabolismus   MeSH
• sekvence aminokyselin MeSH
• terciární struktura proteinů MeSH
• termogeneze fyziologie   MeSH
• transportní proteiny chemie   klasifikace   genetika   metabolismus   MeSH
• uncoupling protein 1 MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• iontové kanály MeSH
• membránové proteiny MeSH
• mitochondriální proteiny MeSH
• rostlinné proteiny MeSH
• transportní proteiny MeSH
• uncoupling protein 1 MeSH