A Molecular Switch in Cytochrome C Oxidase Turns on Thermogenesis in Heart at Low Work Load

Belyanovich, L. M.; Arnold, Susanne; Köhnke, Detlef; Kadenbach, Bernhard

doi:10.1006/bbrc.1996.1830

Cited by 4 publications

(2 citation statements)

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“…In addition, the cardiac muscle mitochondrial metabolic state may control the coupling between electron transport and proton pumping by cytochrome oxidase and thermogenesis. 45 Interestingly, the inhibition of NO biosynthesis in resting conscious dogs increases whole-body O 2 consumption associated with an elevation of body temperature. 46 Thus, an action of NO on cytochrome oxidase may improve the efficiency of O 2 utilization for energy metabolism.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Rat Cardiac Muscle Contraction and Mitochondrial Respiration by Endogenous Peroxynitrite Formation During Posthypoxic Reoxygenation

Xie

Kaminski

Wolin

1998

Circulation Research

105

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Abstract-This study was designed to investigate the potential role of endogenous peroxynitrite (ONOO Ϫ ) formation in the inhibition of cardiac muscle contractility and mitochondrial respiration during posthypoxic reoxygenation. Isometric contraction of isolated rat left ventricular posterior papillary muscle was virtually eliminated at the end of an exposure to 15 minutes of hypoxia and remained 40Ϯ5% depressed an hour after the reintroduction of O 2 . O 2 uptake by rat left ventricular cardiac muscle, measured by a Clark-type O 2 electrode, was also inhibited by 24Ϯ2% at 10 minutes after reoxygenation. The inhibition of contractility and respiration during posthypoxic reoxygenation was markedly attenuated by the NO synthase inhibitor nitro-L-arginine, exogenous superoxide dismutase, and the ONOO Ϫ scavenger urate but not by the hydroxyl radical scavenger mannitol. Generation of ONOO Ϫ with the NO donor S-nitroso-Nacetylpenicillamine (SNAP) plus the superoxide-releasing agent pyrogallol caused an irreversible inhibition of cardiac contractile and respiratory function. Unlike ONOO Ϫ , exogenous (SNAP) and endogenous (bradykinin) sources of NO inhibited contractility in a reversible manner. Under conditions of comparable amounts of respiratory inhibition in unstimulated incubated muscle, the NO-dependent agents and the mitochondrial antagonist NaCN produced a smaller degree of suppression of contractility compared with ONOO Ϫ and posthypoxic reoxygenation. These results are consistent with a contributing role for endogenous ONOO Ϫ formation in the inhibition of cardiac muscle contractility and mitochondrial respiration during posthypoxic reoxygenation. (Circ Res. 1998;82:891-897.)

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Section: Discussionmentioning

confidence: 99%

Inhibition of Rat Cardiac Muscle Contraction and Mitochondrial Respiration by Endogenous Peroxynitrite Formation During Posthypoxic Reoxygenation

Xie

Kaminski

Wolin

1998

Circulation Research

105

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“…Furthermore, at 100% intraliposomal ATP, the H + /e − stoichiometry of a reconstituted enzyme is decreased to half when measured below 98% intraliposomal ATP (more than 2% ADP), which may have physiological consequences in maintaining the body temperature at rest or during sleep, i.e., at low ATP expenditure [23]. Thus, the observed effect of high ATP on CytOx would be expected, which may lead to partial uncoupling of mitochondrial energy transduction and in the stimulation of thermogenesis [24]. Among the three proton pumps of the respiratory chain of mitochondria and bacteria, only CytOx is known to exhibit a slip of proton pumping.…”

Section: Discussionmentioning

confidence: 99%

Cytochrome c Oxidase Inhibition by ATP Decreases Mitochondrial ROS Production

Ramzan

Dolga

Michels

et al. 2022

Cells

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This study addresses the eventual consequence of cytochrome c oxidase (CytOx) inhibition by ATP at high ATP/ADP ratio in isolated rat heart mitochondria. Earlier, it has been demonstrated that the mechanism of allosteric ATP inhibition of CytOx is one of the key regulations of mitochondrial functions. It is relevant that aiming to maintain a high ATP/ADP ratio for the measurement of CytOx activity effectuating the enzymatic inhibition as well as mitochondrial respiration, optimal concentration of mitochondria is critically important. Likewise, only at this concentration, were the differences in ΔΨm and ROS concentrations measured under various conditions significant. Moreover, when CytOx activity was inhibited in the presence of ATP, mitochondrial respiration and ΔΨm both remained static, while the ROS production was markedly decreased. Consubstantial results were found when the electron transport chain was inhibited by antimycin A, letting only CytOx remain functional to support the energy production. This seems to corroborate that the decrease in mitochondrial ROS production is solely the effect of ATP binding to CytOx which results in static respiration as well as membrane potential.

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