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

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