Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox Signaling

0493119 - FGÚ 2019 RIV US eng J - Článek v odborném periodiku
Ježek, Petr - Holendová, Blanka - Garlid, K. D. - Jabůrek, Martin
Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox Signaling.
Antioxidants & Redox Signaling. Roč. 29, č. 7 (2018), s. 667-714. ISSN 1523-0864. E-ISSN 1557-7716
Grant CEP: GA ČR(CZ) GA17-01813S; GA ČR(CZ) GA15-02051S
Institucionální podpora: RVO:67985823
Klíčová slova: mitochondrial uncoupling proteins * UCP2 * fatty acid cycling * attenuation of superoxide formation * redox signaling * anion transport
Obor OECD: Physiology (including cytology)
Impakt faktor: 5.828, rok: 2018

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 Delta p or its potential component, Delta Psi , 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 Delta p dissipation decreases superoxide formation dependent on Delta p. 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.
Trvalý link: http://hdl.handle.net/11104/0286553