Possible Influence of Metabolic Activity on Aging

Kadenbach, Bernhard; Bender, Elisabeth; Reith, Annette; Becker, Andreas; Hammerschmidt, S.; Lee, Icksoo; Arnold, Susanne M.; Hüttemann, Maik

doi:10.1089/rej.1.1999.2.255

Cited by 10 publications

(10 citation statements)

References 47 publications

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“…kinase A switches on the allosteric inhibition of activity at high intramitochondrial ATP/ADP-ratios [4^6]. Similar results are obtained by incubation of isolated mitochondria with cAMP using an endogenous protein kinase (see [18] and Fig. 3).…”

Section: Discussionsupporting

confidence: 60%

“…In a previous paper the increase of ATP-inhibition of solubilized cytochrome c oxidase after preincubation of isolated mitochondria with ATP and cAMP was shown [18]. In the present study the allosteric ATP-inhibition of isolated cytochrome c oxidase from bovine heart was switched on by cAMP-dependent phosphorylation with protein kinase A and ATP.…”

Section: Introductionsupporting

confidence: 54%

“…The possible physiological consequences of the reversible phosphorylation of cytochrome c oxidase has already been discussed in detail [18,28]. Control of respiration by the intramitochondrial ATP/ADP‐ratio via the phosphorylated enzyme is assumed to keep the mitochondrial proton motive force Δ p low, whereas hormone‐induced Ca 2+ ‐dependent dephosphorylation results in loss of respiratory control by the ATP/ADP‐ratio, accompanied by increased respiration and Δ p .…”

Section: Discussionmentioning

confidence: 99%

“…The Ca 2 -ions, however, do not directly interact with cytochrome c oxidase. Furthermore, full inhibition of activity up to 10 WM cytochrome c was obtained after preincubation of mitochondria with potassium £uoride [18], an unspeci¢c inhibitor of protein phosphatases [23].…”

Section: Discussionmentioning

confidence: 99%

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The allosteric ATP‐inhibition of cytochrome c oxidase activity is reversibly switched on by cAMP‐dependent phosphorylation

2000

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In previous studies the allosteric inhibition of cytochrome c oxidase at high intramitochondrial ATP/ADPratios via binding of the nucleotides to the matrix domain of subunit IV was demonstrated. Here we show that the allosteric ATP-inhibition of the isolated bovine heart enzyme is switched on by cAMP-dependent phosphorylation with protein kinase A of subunits II (and/or III) and Vb, and switched off by subsequent incubation with protein phosphatase 1. It is suggested that after cAMP-dependent phosphorylation of cytochrome c oxidase mitochondrial respiration is controlled by the ATP/ADP-ratio keeping the proton motive force v vp low, and the efficiency of energy transduction high. After Ca 2+ -induced dephosphorylation this control is lost, accompanied by increase of v vp, slip of proton pumping (decreased H + /e^stoichiometry), and increase of the rate of respiration and ATP-synthesis at a decreased efficiency of energy transduction.z 2000 Federation of European Biochemical Societies.

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Section: Discussionsupporting

confidence: 60%

Section: Introductionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The allosteric ATP‐inhibition of cytochrome c oxidase activity is reversibly switched on by cAMP‐dependent phosphorylation

2000

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“…The allosteric inhibition by ATP at high intramitochondrial ATP/ADP ratios is hormonally regulated and suggested to prevent the increase of mitochondrial membrane potential and thus the formation of ROS. Some aspects of this hypothesis have been presented before 15, 16…”

Section: Introductionmentioning

confidence: 99%

Cytochrome c Oxidase and the Regulation of Oxidative Phosphorylation

et al. 2001

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Life of higher organisms is essentially dependent on the efficient synthesis of ATP by oxidative phosphorylation in mitochondria. An important and as yet unsolved question of energy metabolism is how are the variable rates of ATP synthesis at maximal work load during exercise or mental work and at rest or during sleep regulated. This article reviews our present knowledge on the structure of bacterial and eukaryotic cytochrome c oxidases and correlates it with recent results on the regulatory functions of nuclear-coded subunits of the eukaryotic enzyme, which are absent from the bacterial enzyme. A new molecular hypothesis on the physiological regulation of oxidative phosphorylation is proposed, assuming a hormonally controlled dynamic equilibrium in vivo between two states of energy metabolism, a relaxed state with low ROS (reactive oxygen species) formation, and an excited state with elevated formation of ROS, which are known to accelerate aging and to cause degenerative diseases and cancer. The hypothesis is based on the allosteric ATP inhibition of cytochrome c oxidase at high intramitochondrial ATP/ADP ratios ("second mechanism of respiratory control"), which is switched on by cAMP-dependent phosphorylation and switched off by calcium-induced dephosphorylation of the enzyme.

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The Ubiquinol/bc1 Redox Couple Regulates Mitochondrial Oxygen Radical Formation

Gille

Nohl

2001

Archives of Biochemistry and Biophysics

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Possible Influence of Metabolic Activity on Aging

Cited by 10 publications

References 47 publications

The allosteric ATP‐inhibition of cytochrome c oxidase activity is reversibly switched on by cAMP‐dependent phosphorylation

The allosteric ATP‐inhibition of cytochrome c oxidase activity is reversibly switched on by cAMP‐dependent phosphorylation

Cytochrome c Oxidase and the Regulation of Oxidative Phosphorylation

The Ubiquinol/bc1 Redox Couple Regulates Mitochondrial Oxygen Radical Formation

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