Difference between revisions of "Plecita-Hlavata 2009 Int J Biochem Cell Biol"

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Plecita-Hlavata L, Jezek J, Jezek P (2009) Pro-oxidant mitochondrial matrix-targeted ubiquinone MitoQ₁₀ acts as anti-oxidant at retarded electron transport or proton pumping within Complex I. Int J Biochem Cell Biol 41:1697-707.

» PMID: 19433311

Plecita-Hlavata L, Jezek J, Jezek P (2009) Int J Biochem Cell Biol

Abstract: Oxidative stress of mitochondrial origin, i.e. elevated mitochondrial superoxide production, belongs to major factors determining aging and oxidative-stress-related diseases. Antioxidants, such as the mitochondria-targeted coenzyme Q, MitoQ₁₀, may prevent or cure these pathological conditions. To elucidate pro- and anti-oxidant action of MitoQ₁₀, we studied its effects on HepG2 cell respiration, mitochondrial network morphology, and rates of superoxide release (above that neutralized by superoxide dismutase) to the mitochondrial matrix (J_m). MitoSOX Red fluorescence confocal microscopy monitoring of J_m rates showed pro-oxidant effects of 3.5-fold increased J_m with MitoQ₁₀. MitoQ₁₀ induced fission of the mitochondrial network which was recovered after 24 h. In rotenone-inhibited HepG2 cells (i.e., already under oxidative stress) MitoQ₁₀ sharply decreased rotenone-induced J_m, but not together with the Complex II inhibitor thenoyltrifluoroacetone. Respiration of HepG2 cells and isolated rat liver mitochondria with MitoQ₁₀ increased independently of rotenone. The increase was prevented by thenoyltrifluoroacetone. These results suggest that MitoQ₁₀ accepts electrons prior to the rotenone-bound Q-site, and the Complex II reverse mode oxidizes MitoQ₁₀H₂ to regenerate MitoQ₁₀. Consequently, MitoQ₁₀ has a pro-oxidant role in intact cells, whereas it serves as an antioxidant when Complex I-derived superoxide generation is already elevated due to electron flow retardation. Moreover, unlike mitochondrial uncoupling, MitoQ₁₀ exerted its antioxidant role when Complex I proton pumping was retarded by a hydrophobic amiloride, 5-(N-ethyl-N-isopropyl) amiloride. Consequently, MitoQ₁₀ may be useful in the treatment of diseases originating from impairment of respiratory chain Complex I due to oxidatively damaged mitochondrial DNA, when its targeted delivery to pathogenic tissues is ensured. • Keywords: Mitochondria-targeted antioxidants, Mitochondrial Complex I, Mitochondrial matrix superoxide release, Mitochondrial network morphology

• O2k-Network Lab: CZ Prague Jezek P

Labels:

Stress:Oxidative stress;RONS Organism: Rat Tissue;cell: Liver Preparation: Isolated mitochondria

HRR: Oxygraph-2k

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 {{Publication
-|title=Plecita-Hlavata L, Jezek J, Jezek P (2009) Pro-oxidant mitochondrial matrix-targeted ubiquinone MitoQ10 acts as anti-oxidant at retarded electron transport or proton pumping within Complex I. Int J Biochem Cell Biol 41:1697-1707.
+|title=Plecita-Hlavata L, Jezek J, Jezek P (2009) Pro-oxidant mitochondrial matrix-targeted ubiquinone MitoQ<sub>10</sub> acts as anti-oxidant at retarded electron transport or proton pumping within Complex I. Int J Biochem Cell Biol 41:1697-707.
 |info=[http://www.ncbi.nlm.nih.gov/pubmed/19433311 PMID: 19433311]
 |authors=Plecita-Hlavata L, Jezek J, Jezek P
 |year=2009
 |journal=Int J Biochem Cell Biol
-|abstract=Oxidative stress of mitochondrial origin, i.e. elevated mitochondrial superoxide production, belongs to major factors determining aging and oxidative-stress-related diseases. Antioxidants, such as the mitochondria-targeted coenzyme Q, MitoQ10, may prevent or cure these pathological conditions. To elucidate pro- and anti-oxidant action of MitoQ10, we studied its effects on HepG2 cell respiration, mitochondrial network morphology, and rates of superoxide release (above that neutralized by superoxide dismutase) to the mitochondrial matrix (Jm). MitoSOX Red fluorescence confocal microscopy monitoring of Jm rates showed pro-oxidant effects of 3.5-fold increased Jm with MitoQ10. MitoQ10  induced fission of the mitochondrial network which was recovered after 24 h. In rotenone-inhibited HepG2 cells (i.e., already under oxidative stress) MitoQ10 sharply decreased rotenone-induced Jm, but not together with the Complex II inhibitor thenoyltrifluoroacetone. Respiration of HepG2 cells and isolated rat liver mitochondria with MitoQ10 increased independently of rotenone. The increase was prevented by thenoyltrifluoroacetone. These results suggest that MitoQ10 accepts electrons prior to the rotenone-bound Q-site, and the Complex II reverse mode oxidizes MitoQ10H2 to regenerate MitoQ10. Consequently, MitoQ10  has a pro-oxidant role in intact cells, whereas it serves as an antioxidant when Complex I-derived superoxide generation is already elevated due to electron flow retardation. Moreover, unlike mitochondrial uncoupling, MitoQ10 exerted its antioxidant role when Complex I proton pumping was retarded by a hydrophobic amiloride, 5-(N-ethyl-N-isopropyl) amiloride. Consequently, MitoQ10  may be useful in the treatment of diseases originating from impairment of respiratory chain Complex I due to oxidatively damaged mitochondrial DNA, when its targeted delivery to pathogenic tissues is ensured.
+|abstract=Oxidative stress of mitochondrial origin, i.e. elevated mitochondrial superoxide production, belongs to major factors determining aging and oxidative-stress-related diseases. Antioxidants, such as the mitochondria-targeted coenzyme Q, MitoQ<sub>10</sub>, may prevent or cure these pathological conditions. To elucidate pro- and anti-oxidant action of MitoQ<sub>10</sub>, we studied its effects on HepG2 cell respiration, mitochondrial network morphology, and rates of superoxide release (above that neutralized by superoxide dismutase) to the mitochondrial matrix (''J''<sub>m</sub>). MitoSOX Red fluorescence confocal microscopy monitoring of ''J''<sub>m</sub> rates showed pro-oxidant effects of 3.5-fold increased ''J''<sub>m</sub> with MitoQ<sub>10</sub>. MitoQ<sub>10</sub> induced fission of the mitochondrial network which was recovered after 24 h. In rotenone-inhibited HepG2 cells (i.e., already under oxidative stress) MitoQ<sub>10</sub> sharply decreased rotenone-induced ''J''<sub>m</sub>, but not together with the Complex II inhibitor thenoyltrifluoroacetone. Respiration of HepG2 cells and isolated rat liver mitochondria with MitoQ<sub>10</sub> increased independently of rotenone. The increase was prevented by thenoyltrifluoroacetone. These results suggest that MitoQ<sub>10</sub> accepts electrons prior to the rotenone-bound Q-site, and the Complex II reverse mode oxidizes MitoQ<sub>10</sub>H<sub>2</sub> to regenerate MitoQ<sub>10</sub>. Consequently, MitoQ<sub>10</sub>  has a pro-oxidant role in intact cells, whereas it serves as an antioxidant when Complex I-derived superoxide generation is already elevated due to electron flow retardation. Moreover, unlike mitochondrial uncoupling, MitoQ<sub>10</sub> exerted its antioxidant role when Complex I proton pumping was retarded by a hydrophobic amiloride, 5-(N-ethyl-N-isopropyl) amiloride. Consequently, MitoQ<sub>10</sub>  may be useful in the treatment of diseases originating from impairment of respiratory chain Complex I due to oxidatively damaged mitochondrial DNA, when its targeted delivery to pathogenic tissues is ensured.
 |keywords=Mitochondria-targeted antioxidants, Mitochondrial Complex I, Mitochondrial matrix superoxide release, Mitochondrial network morphology
 |mipnetlab=CZ Prague Jezek P