Cell Respiration is Controlled by ATP, an Allosteric Inhibitor of Cytochrome‐<i>c</i> Oxidase

Arnold, Susanne; Kadenbach, Bernhard

doi:10.1111/j.1432-1033.1997.t01-1-00350.x

Cited by 207 publications

(190 citation statements)

References 45 publications

Supporting

Mentioning

182

Contrasting

Unclassified

Order By: Relevance

“…In contrast to the external effect, the matrix-oriented inhibition of ATP is extensively documented in the literature for eucaryotic COX including yeast (80). There is strong evidence that this effect is linked to the cooperative binding of ferrocytochrome c to the dimeric enzyme, which can be abolished by decreasing the ATP/ADP (22,49,51,80). In addition to the effect on enzyme turnover, adenylic nucleotides seem to modulate the proton pumping ef ciency of isolated mammalian COX in a tissue-speci c manner (16,27).…”

Section: Discussionmentioning

confidence: 99%

“…Hence, the sigmoidal substrate/activity relationship is a consequence of cooperative interaction between the two cytochrome c binding sites in the dimeric enzyme complex (i.e., Hill coef cient equals 2). Because cooperativity inevitably involves binding and dissociation of cytochrome c, it is lost when the COX activity is measured in the presence of TMPD as a direct electron donor to bound ferricytochrome c. Moreover, cooperativity is also lost when the enzyme is solubilized by dodecyl maltoside (49), which is known to monomerize the isolated enzyme and thus prevents cooperative interactions of the dimeric enzyme complex. Finally, the allosteric inhibition of the Tween 80-solubilized enzyme by ATP is abolished after preincubation with a monoclonal antibody against subunit IV (49).…”

Section: Allosteric Inhibition Of Cox By High Internal Atp/adpmentioning

confidence: 99%

“…Because cooperativity inevitably involves binding and dissociation of cytochrome c, it is lost when the COX activity is measured in the presence of TMPD as a direct electron donor to bound ferricytochrome c. Moreover, cooperativity is also lost when the enzyme is solubilized by dodecyl maltoside (49), which is known to monomerize the isolated enzyme and thus prevents cooperative interactions of the dimeric enzyme complex. Finally, the allosteric inhibition of the Tween 80-solubilized enzyme by ATP is abolished after preincubation with a monoclonal antibody against subunit IV (49). In parallel, it has been demonstrated that the exchange of bound ATP against ADP induces large spectral changes within COX solubilized with Tween 80, in contrast to dodecyl maltoside.…”

Section: Allosteric Inhibition Of Cox By High Internal Atp/adpmentioning

confidence: 99%

“…The ascorbate-mediated respiration of Tween 80-solubilized COX was measured polarographically at increasing concentrations of ferrocytochrome c, in the presence of an ATP-regenerating system to modulate the ATP/ADP ratio (49). In the presence of high ATP/ADP ratios, a sigmoidal titration curve was obtained, with complete inhibition of COX activity up to 4 ¹M cytochrome c. With decreasing ATP/ADP ratios, the sigmoidal titration curve became hyperbolic and the maximal COX activity measured at saturating amounts of cytochrome c largely increased.…”

Section: Allosteric Inhibition Of Cox By High Internal Atp/adpmentioning

confidence: 99%

See 3 more Smart Citations

Regulation of Cytochrome c Oxidase by Adenylic Nucleotides. Is Oxidative Phosphorylation Feedback Regulated by its End‐Products?

Beauvoit¹,

Rigoulet²

2001

IUBMB Life

View full text Add to dashboard Cite

SummaryCytochrome c oxidase, which catalyzes an irreversible step of the respiratory chain, is one of the rate-controlling steps of oxidative phosphorylation on isolated mitochondria. The rate of electron transfer through the complex is primarily controlled by the associated thermodynamic forces, i.e., the span in redox potential between oxygen and cytochrome c and the protonmotive force. However, the electron ux also depends on the various kinetic effectors, including adenylic nucleotides. Although the number of binding sites for ATP and ADP on cytochrome oxidase is still a matter of debate, experiments performed on the solubilized and reconstituted enzyme provide strong functional evidence that the mammalian cytochrome c oxidase binds adenylic nucleotides on both sides of the inner membrane. These effects include modi cation in cytochrome c af nity, allosteric inhibition and changes in proton pumping ef ciency. Immunological studies have pointed out the role of subunit IV and that of an ATP-binding protein, subunit VIa, in these kinetic regulations. In yeast, the role of the nuclear-encoded subunits in assembly and regulation of the cytochrome c oxidase has been further substantiated by using gene-disruption analysis. Using a subunit VIa-null mutant, the consequences of the ATP regulation on oxidative phosphorylation have been further investigated on isolated mitochondria. Taken together, the data demonstrate that there are multiple regulating sites for ATP on the yeast cytochrome oxidase with respect to the location (matrix versus cytosolic side), kinetic effect (activation versus inhibition) and consequence on the ow-force relationships. The question is therefore raised as to the

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Allosteric Inhibition Of Cox By High Internal Atp/adpmentioning

confidence: 99%

Section: Allosteric Inhibition Of Cox By High Internal Atp/adpmentioning

confidence: 99%

Section: Allosteric Inhibition Of Cox By High Internal Atp/adpmentioning

confidence: 99%

See 2 more Smart Citations

Regulation of Cytochrome c Oxidase by Adenylic Nucleotides. Is Oxidative Phosphorylation Feedback Regulated by its End‐Products?

Beauvoit¹,

Rigoulet²

2001

IUBMB Life

View full text Add to dashboard Cite

show abstract

“…Arnold and Kadenbach have shown that high intramitochondrial ATP/ADP ratios convert the hyperbolic kinetics of ascorbate‐dependent respiration of isolated CytOx to an inhibited allosteric kinetic status (Hill coefficient >1), which is independent of the Ψm and is based on the binding of ATP or ADP to the matrix domain of CytOx subunit IV 72. Ogbi et al 73 observed that phosphorylation of CytOx subunit IV by protein kinase Cϵ produced an increase in the CytOx activity.…”

Section: Ros Have Double Functionsmentioning

confidence: 99%

Revisiting Kadenbach: Electron flux rate through cytochrome c‐oxidase determines the ATP‐inhibitory effect and subsequent production of ROS

et al. 2016

View full text Add to dashboard Cite

Mitochondrial respiration is the predominant source of ATP. Excessive rates of electron transport cause a higher production of harmful reactive oxygen species (ROS). There are two regulatory mechanisms known. The first, according to Mitchel, is dependent on the mitochondrial membrane potential that drives ATP synthase for ATP production, and the second, the Kadenbach mechanism, is focussed on the binding of ATP to Cytochrome c Oxidase (CytOx) at high ATP/ADP ratios, which results in an allosteric conformational change to CytOx, causing inhibition. In times of stress, ATP‐dependent inhibition is switched off and the activity of CytOx is exclusively determined by the membrane potential, leading to an increase in ROS production. The second mechanism for respiratory control depends on the quantity of electron transfer to the Heme aa3 of CytOx. When ATP is bound to CytOx the enzyme is inhibited, and ROS formation is decreased, although the mitochondrial membrane potential is increased.

show abstract

Cytochrome c Oxidase and the Regulation of Oxidative Phosphorylation

et al. 2001

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Cell Respiration is Controlled by ATP, an Allosteric Inhibitor of Cytochrome‐c Oxidase

Cited by 207 publications

References 45 publications

Regulation of Cytochrome c Oxidase by Adenylic Nucleotides. Is Oxidative Phosphorylation Feedback Regulated by its End‐Products?

Regulation of Cytochrome c Oxidase by Adenylic Nucleotides. Is Oxidative Phosphorylation Feedback Regulated by its End‐Products?

Revisiting Kadenbach: Electron flux rate through cytochrome c‐oxidase determines the ATP‐inhibitory effect and subsequent production of ROS

Cytochrome c Oxidase and the Regulation of Oxidative Phosphorylation

Contact Info

Product

Resources

About