SIGNIFICANCE: Mitochondria are the energetic, metabolic, redox, and information signaling centers of the cell. Substrate pressure, mitochondrial network dynamics, and cristae morphology state are integrated by the protonmotive force Δp or its potential component, ΔΨ, which are attenuated by proton backflux into the matrix, termed uncoupling. The mitochondrial uncoupling proteins (UCP1-5) play an eminent role in the regulation of each of the mentioned aspects, being involved in numerous physiological events including redox signaling. Recent Advances: UCP2 structure, including purine nucleotide and fatty acid (FA) binding sites, strongly support the FA cycling mechanism: UCP2 expels FA anions, whereas uncoupling is achieved by the membrane backflux of protonated FA. Nascent FAs, cleaved by phospholipases, are preferential. The resulting Δp dissipation decreases superoxide formation dependent on Δp. UCP-mediated antioxidant protection and its impairment are expected to play a major role in cell physiology and pathology. Moreover, UCP2-mediated aspartate, oxaloacetate, and malate antiport with phosphate is expected to alter metabolism of cancer cells. CRITICAL ISSUES: A wide range of UCP antioxidant effects and participations in redox signaling have been reported; however, mechanisms of UCP activation are still debated. Switching off/on the UCP2 protonophoretic function might serve as redox signaling either by employing/releasing the extra capacity of cell antioxidant systems or by directly increasing/decreasing mitochondrial superoxide sources. Rapid UCP2 degradation, FA levels, elevation of purine nucleotides, decreased Mg2+, or increased pyruvate accumulation may initiate UCP-mediated redox signaling. FUTURE DIRECTIONS: Issues such as UCP2 participation in glucose sensing, neuronal (synaptic) function, and immune cell activation should be elucidated. Antioxid. Redox Signal. 29, 667-714.

• Klíčová slova
• UCP2, anion transport, attenuation of superoxide formation, fatty acid cycling, mitochondrial uncoupling proteins, redox signaling,
• MeSH
• antioxidancia metabolismus   MeSH
• lidé MeSH
• mitochondriální odpřahující proteiny metabolismus   MeSH
• oxidace-redukce MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antioxidancia MeSH
• mitochondriální odpřahující proteiny MeSH

Mitochondria play a key role in energy metabolism in many tissues, including cardiac and skeletal muscle, brain, liver, and adipose tissue. Three types of adipose depots can be identified in mammals, commonly classified according to their colour appearance: the white (WAT), the brown (BAT), and the beige/brite/brown-like (bAT) adipose tissues. WAT is mainly involved in the storage and mobilization of energy and BAT is predominantly responsible for nonshivering thermogenesis. Recent data suggest that adipocyte mitochondria might play an important role in the development of obesity through defects in mitochondrial lipogenesis and lipolysis, regulation of adipocyte differentiation, apoptosis, production of oxygen radicals, efficiency of oxidative phosphorylation, and regulation of conversion of white adipocytes into brown-like adipocytes. This review summarizes the main characteristics of each adipose tissue subtype and describes morphological and functional modifications focusing on mitochondria and their activity in healthy and unhealthy adipocytes.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Existing controversies led us to analyze absolute mRNA levels of mitochondrial uncoupling proteins (UCP1-UCP5). Individual UCP isoform mRNA levels varied by up to four orders of magnitude in rat and mouse tissues. UCP2 mRNA content was relatively high (0.4 to 0.8 pg per 10 ng of total mRNA) in rat spleen, rat and mouse lung, and rat heart. Levels of the same order of magnitude were found for UCP3 mRNA in rat and mouse skeletal muscle, for UCP4 and UCP5 mRNA in mouse brain, and for UCP2 and UCP5 mRNA in mouse white adipose tissue. Significant differences in pattern were found for rat vs. mouse tissues, such as the dominance of UCP3/UCP5 vs. UCP2 transcript in mouse heart and vice versa in rat heart; or UCP2 (UCP5) dominance in rat brain contrary to 10-fold higher UCP4 and UCP5 dominance in mouse brain. We predict high antioxidant/antiapoptotic UCP function in tissues with higher UCP mRNA content.

• MeSH
• DNA primery genetika   MeSH
• druhová specificita MeSH
• iontové kanály metabolismus   MeSH
• krysa rodu Rattus MeSH
• membránové transportní proteiny metabolismus   MeSH
• messenger RNA metabolismus   MeSH
• mitochondriální odpřahující proteiny MeSH
• mitochondriální proteiny metabolismus   MeSH
• mozek metabolismus   MeSH
• myokard metabolismus   MeSH
• myši MeSH
• plíce metabolismus   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• proteiny nervové tkáně metabolismus   MeSH
• slezina metabolismus   MeSH
• transportní proteiny mitochondriální membrány MeSH
• uncoupling protein 2 MeSH
• uncoupling protein 3 MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• DNA primery MeSH
• iontové kanály MeSH
• membránové transportní proteiny MeSH
• messenger RNA MeSH
• mitochondriální odpřahující proteiny MeSH
• mitochondriální proteiny MeSH
• proteiny nervové tkáně MeSH
• Slc25a14 protein, rat MeSH Prohlížeč
• Slc25a27 protein, rat MeSH Prohlížeč
• transportní proteiny mitochondriální membrány MeSH
• Ucp2 protein, mouse MeSH Prohlížeč
• Ucp2 protein, rat MeSH Prohlížeč
• Ucp3 protein, mouse MeSH Prohlížeč
• Ucp3 protein, rat MeSH Prohlížeč
• uncoupling protein 2 MeSH
• uncoupling protein 3 MeSH

In vitro experiments suggest that stimulation of lipolysis by catecholamines in adipocytes depends on the energy status of these cells. We tested whether mitochondrial uncoupling proteins (UCPs) that control the efficiency of ATP production could affect lipolysis and noradrenaline signalling in white fat in vivo. The lipolytic effect of noradrenaline was lowered by ectopic UCP1 in white adipocytes of aP2-Ucp1 transgenic mice, overexpressing the UCP1 gene from the aP2 gene promoter, reflecting the magnitude of UCP1 expression, the impaired stimulation of cAMP levels by noradrenaline and the reduction of the ATP/ADP ratio in different fat depots. Thus only subcutaneous but not epididymal fat was affected. UCP1 also down-regulated the expression of hormone-sensitive lipase and lowered its activity, and altered the expression of trimeric G-proteins in adipocytes. The adipose tissue content of the stimulatory G-protein alpha subunit was increased while that of the inhibitory G-protein alpha subunits decreased in response to UCP1 expression. Our results support the idea that the energy status of cells, and the ATP/ADP ratio in particular, modulates the lipolytic effects of noradrenaline in adipose tissue in vivo. They also demonstrate changes at the G-protein level that tend to overcome the reduction of lipolysis when ATP level in adipocytes is low. Therefore, respiratory uncoupling may exert a broad effect on hormonal signalling in adipocytes.

• MeSH
• adenosindifosfát metabolismus   MeSH
• adenosintrifosfát metabolismus   MeSH
• AMP cyklický metabolismus   MeSH
• DNA primery MeSH
• genotyp MeSH
• hepatocyty enzymologie   MeSH
• iontové kanály MeSH
• lipasa genetika   MeSH
• lipolýza * MeSH
• membránové proteiny genetika   fyziologie   MeSH
• mitochondriální proteiny MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• noradrenalin metabolismus   MeSH
• proteiny vázající GTP metabolismus   MeSH
• regulace genové exprese enzymů MeSH
• sekvence nukleotidů MeSH
• transportní proteiny genetika   fyziologie   MeSH
• tuková tkáň enzymologie   metabolismus   MeSH
• uncoupling protein 1 MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosindifosfát MeSH
• adenosintrifosfát MeSH
• AMP cyklický MeSH
• DNA primery MeSH
• iontové kanály MeSH
• lipasa MeSH
• membránové proteiny MeSH
• mitochondriální proteiny MeSH
• noradrenalin MeSH
• proteiny vázající GTP MeSH
• transportní proteiny MeSH
• Ucp1 protein, mouse MeSH Prohlížeč
• uncoupling protein 1 MeSH