Inhibition of electron and energy transfer in mitochondria by 19-nor-ethynyltestosterone acetate

Boveris, Alberto; Stoppani, A. O. M.

doi:10.1016/0003-9861(70)90184-0

Cited by 29 publications

(8 citation statements)

References 33 publications

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“…2A, trace c). In the former instances, ubiquinol is the likely electron donor for Reaction 1; the rate constant of this reaction may be estimated as 2.1 ϫ 10 3 M -1 s -1 based on an ubiquinol content of ϳ2 nmol/mg of mitochondrial protein under these experimental conditions (36). In the latter instances-in absence of myxothiazol-reduction of cytochrome c (Reaction 3) and cytochrome oxidase (Reaction 4) also contribute to ⅐NO decay via a reductive pathway.…”

Section: Effects Of ⅐No On Mitochondrial Respiration-⅐no Utilizationmentioning

confidence: 99%

The Regulation of Mitochondrial Oxygen Uptake by Redox Reactions Involving Nitric Oxide and Ubiquinol

Poderoso¹,

Lisdero²,

Schöpfer³

et al. 1999

Journal of Biological Chemistry

172

130

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The reversible inhibitory effects of nitric oxide (⅐NO) on mitochondrial cytochrome oxidase and O 2 uptake are dependent on intramitochondrial ⅐NO utilization. This study was aimed at establishing the mitochondrial pathways for In the early 1970s, it was recognized that isolated respiring mitochondria produce hydrogen peroxide (H 2 O 2 ) at rates that depend on the redox state of the components of the respiratory chain and, consequently, on the mitochondrial metabolic state and the presence of inhibitors (1, 2). Mitochondrial production of H 2 O 2 accounts for about 1% of the O 2 uptake under physiological conditions, according to evidence obtained from perfused rat liver and heart (3). Mitochondrial H 2 O 2 is produced through the manganese-superoxide dismutase-catalyzed disproportionation of O 2. (4 -6), which is vectorially generated into the mitochondrial matrix during ubisemiquinone autoxidation (4, 7, 8) and NADH-dehydrogenase activity (9 value of 0.5-1.0 ϫ 10 -10 M can be estimated (3, 10). Nitric oxide (⅐NO) produced by the endothelium elicits cellular physiological effects within a wide concentration range (10 -9 to 10 -5 M). The effects of ⅐NO on mitochondria-inhibition of cytochrome c oxidase (11-19), impairment of electron flow at the cytochrome bc 1 region (17), and oxidation of ubiquinol (20, 21)-require progressively increasing concentrations of this species. ⅐NO regulates O 2 uptake and promotes H 2 O 2 release by mitochondria (17,22) (an effect also demonstrated in the isolated beating rat heart (23)); the increase in mitochondrial H 2 O 2 formation may be understood as an antimycin-like effect of ⅐NO accomplished by its effective binding to the cytochrome bc 1 segment (17).The ⅐NO influx in the mitochondrial compartment is expected to affect the steady-state levels of O 2 . due to the diffusion-controlled reaction between these species (24, 25) to yield peroxynitrite (ONOO -) (26). Three recently recognized facts add complexity to the mitochondrial interactions between O 2 .and ⅐NO: first, ⅐NO inhibits succinate-cytochrome c reductase activity and increases O 2 . production in submitochondrial particles, isolated mitochondria, and perfused rat heart (17, 23). Second, membrane-bound mitochondrial NOS 1 generates ⅐NO at rates that are similar to the rates of mitochondrial O 2 . production (27-29). Third, ⅐NO can be reduced to the nitroxyl anion (NO -) by one-electron transfers from three reduced components of the mitochondrial respiratory chain: ubiquinol, cytochrome c, and cytochrome c oxidase (20,30,31).The fine metabolic control of the intramitochondrial steadystate concentrations of ⅐NO-performed through a series of oxidative and reductive reactions involving O 2 . , ubiquinol, the cytochrome bc 1 segment, and cytochrome c oxidase-is relevant to mitochondrial physiology with further implications for cell energy production. This study is aimed at establishing the mitochondrial pathways for ⅐NO utilization that regulate O 2 .generation via reductive and oxidative reactions involving ubiquinol...

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Section: Effects Of ⅐No On Mitochondrial Respiration-⅐no Utilizationmentioning

confidence: 99%

The Regulation of Mitochondrial Oxygen Uptake by Redox Reactions Involving Nitric Oxide and Ubiquinol

Poderoso¹,

Lisdero²,

Schöpfer³

et al. 1999

Journal of Biological Chemistry

172

130

View full text Add to dashboard Cite

show abstract

“…NADH dehydrogenase, a complex of at least 42 polypeptides ($ 900 kDa), constitutes Complex I and succinate dehydrogenase (120 kDa) constitutes Complex II [1]. NADH dehydrogenase was found to be more sensitive than succinate dehydrogenase when exposed to membrane-modifying agents, such as steroids and lysophospholipids [2][3][4]. Complex I was also more sensitive than Complex II in cancer cells that were exposed to macrophages ; isolated mitochondria exhibited specific damage in NADHdehydrogenase-dependent O # uptake due to the cytotoxic molecules, later recognized as peroxynitrite anion (ONOO − ), released by the macrophages [5,6].…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide inhibits mitochondrial NADH:ubiquinone reductase activity through peroxynitrite formation

Riobo

Clementi

Melani

et al. 2001

Biochemical Journal

146

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This study was aimed at assessing the effects of long-term exposure to NO of respiratory activities in mitochondria from different tissues (with different ubiquinol contents), under conditions that either promote or prevent the formation of peroxynitrite. Mitochondria and submitochondrial particles isolated from rat heart, liver and brain were exposed either to a steady-state concentration or to a bolus addition of NO. NO induced the mitochondrial production of superoxide anions, hydrogen peroxide and peroxynitrite, the latter shown by nitration of mitochondrial proteins. Long-term incubation of mitochondrial membranes with NO resulted in a persistent inhibition of NADH:cytochrome c reductase activity, interpreted as inhibition of NADH:ubiquinone reductase (Complex I) activity, whereas succinate:cytochrome c reductase activity, including Complex II and Complex III electron transfer, remained unaffected. This selective effect of NO and derived species was partially prevented by superoxide dismutase and uric acid. In addition, peroxynitrite mimicked the effect of NO, including tyrosine nitration of some Complex I proteins. These results seem to indicate that the inhibition of NADH:ubiquinone reductase (Complex I) activity depends on the NO-induced generation of superoxide radical and peroxynitrite and that Complex I is selectively sensitive to peroxynitrite. Inhibition of Complex I activity by peroxynitrite may have critical implications for energy supply in tissues such as the brain, whose mitochondrial function depends largely on the channelling of reducing equivalents through Complex I.

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“…Ubiquinol and cytochrome aa 3 contents were taken as 277µM and 5.6µM, respectively, considering a mitochondrial matrix volume of 7.0µl×mg protein -1 . 66,69 Once the O 2 and NO steady-state concentrations were calculated, the ONOOproduction rate was estimated from Eq. 3, taking into account the second-order rate constant k 1 :…”

Section: ###mentioning

confidence: 99%

Mitochondrial peroxynitrite generation is mainly driven by superoxide steady-state concentration rather than by nitric oxide steady-state concentration

Valdez

Bombicino

Iglesias

et al. 2018

IJMBOA

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Inhibition of electron and energy transfer in mitochondria by 19-nor-ethynyltestosterone acetate

Cited by 29 publications

References 33 publications

The Regulation of Mitochondrial Oxygen Uptake by Redox Reactions Involving Nitric Oxide and Ubiquinol

The Regulation of Mitochondrial Oxygen Uptake by Redox Reactions Involving Nitric Oxide and Ubiquinol

Nitric oxide inhibits mitochondrial NADH:ubiquinone reductase activity through peroxynitrite formation

Mitochondrial peroxynitrite generation is mainly driven by superoxide steady-state concentration rather than by nitric oxide steady-state concentration

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