Cell respiration is controlled by ATP, an allosteric inhibitor of cytochrome-c oxidase.

The activity of cytochrome-c oxidase, the terminal enzyme of the mitochondrial respiratory chain, is known to be regulated by the substrate pressure, i.e. the ferro-/ferricytochrome c ratio, by the oxygen concentration, and by the electrochemical proton gradient delta muH+ across the inner mitochondrial membrane. Here we describe a further mechanism of 'respiratory control' via allosteric inhibition of cytochrome-c oxidase by ATP, which binds to the matrix domain, of subunit IV. The cooperativity between cytochrome-c-binding sites in the dimeric enzyme complex is mediated by cardiolipin, which is essential for cooperativity of the enzyme within the lipid membrane.

[1]  F. Lottspeich,et al.  The subunit structure of cytochrome-c oxidase from tuna heart and liver. , 1997, European journal of biochemistry.

[2]  H A Krebs,et al.  Cytosolic phosphorylation potential. , 1979, The Journal of biological chemistry.

[3]  D. Thompson,et al.  The functional and physical form of mammalian cytochrome c oxidase determined by gel filtration, radiation inactivation, and sedimentation equilibrium analysis. , 1984, The Journal of biological chemistry.

[4]  A. From,et al.  Regulation of the oxidative phosphorylation rate in the intact cell. , 1990, Biochemistry.

[5]  B. Kadenbach,et al.  ADP increases the affinity for cytochrome c by interaction with the matrix side of bovine heart cytochrome c oxidase. , 1987, Biochemical and biophysical research communications.

[6]  G. Striker,et al.  Insulin uptake and processing by cultured mouse glomerular endothelial cells. , 1993, The American journal of physiology.

[7]  H. Lardy,et al.  Oxidative phosphorylations; rôle of inorganic phosphate and acceptor systems in control of metabolic rates. , 1952, The Journal of biological chemistry.

[8]  T. Tomizaki,et al.  Structures of metal sites of oxidized bovine heart cytochrome c oxidase at 2.8 A , 1995, Science.

[9]  H. Dekker,et al.  Separation, stability and kinetics of monomeric and dimeric bovine heart cytochrome c oxidase. , 1987, Biochimica et biophysica acta.

[10]  R. Balaban,et al.  NMR studies of renal phosphate metabolites in vivo: effects of hydration and dehydration. , 1988, The American journal of physiology.

[11]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[12]  M. Fabian,et al.  The reaction of cyanide with peroxidatic forms of cytochrome oxidase. , 1995, Biochemistry.

[13]  N. C. Robinson,et al.  Functional binding of cardiolipin to cytochromec oxidase , 1993, Journal of bioenergetics and biomembranes.

[14]  C. Wallace,et al.  The oxidation-state-dependent ATP-binding site of cytochrome c. A possible physiological significance. , 1986, The Biochemical journal.

[15]  A. Koretsky,et al.  Respiratory control in the glucose perfused heart , 1987, FEBS letters.

[16]  H. Kolbe,et al.  The mitochondrial phosphate carrier has an essential requirement for cardiolipin , 1982, FEBS letters.

[17]  M. Haas,et al.  Stimulation of K-C1 cotransport in rat red cells by a hemolytic anemia-producing metabolite of dapsone. , 1989, The American journal of physiology.

[18]  T. Tomizaki,et al.  The Whole Structure of the 13-Subunit Oxidized Cytochrome c Oxidase at 2.8 Å , 1996, Science.

[19]  W. Caughey,et al.  Crystalline cytochrome c oxidase of bovine heart mitochondrial membrane: composition and x-ray diffraction studies. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[20]  F. Palmieri,et al.  Functional properties of purified and reconstituted mitochondrial metabolite carriers , 1993, Journal of bioenergetics and biomembranes.

[21]  G. Krishnamoorthy,et al.  Non-ohmic proton conductance of mitochondria and liposomes. , 1984, Biochemistry.

[22]  R. Balaban.  The application of nuclear magnetic resonance to the study of cellular physiology. , 1984, The American journal of physiology.

[23]  G. Pielak,et al.  Design of a Ruthenium-Cytochrome c Derivative to Measure Electron Transfer to the Initial Acceptor in Cytochrome c Oxidase (*) , 1995, The Journal of Biological Chemistry.

[24]  S. Yoshikawa,et al.  ATP and ADP Bind to Cytochrome c Oxidase and Regulate Its Activity , 1997, Biological chemistry.

[25]  A. Azzi,et al.  The interconversion between monomeric and dimeric bovine heart cytochrome c oxidase. , 1985, Biochimie.

[26]  E. Margoliash,et al.  Definition of cytochrome c binding domains by chemical modification. III. Kinetics of reaction of carboxydinitrophenyl cytochromes c with cytochrome c oxidase. , 1978, The Journal of biological chemistry.

[27]  R S Balaban,et al.  Relation between phosphate metabolites and oxygen consumption of heart in vivo. , 1989, The American journal of physiology.

[28]  R S Balaban,et al.  Regulation of oxidative phosphorylation in the mammalian cell. , 1990, The American journal of physiology.

[29]  G. Salama,et al.  Effects of cardiac work on electrical potential gradient across mitochondrial membrane in perfused rat hearts. , 1993, The American journal of physiology.

[30]  A. Azzi,et al.  Studies on the transmembrane orientation of cytochrome c oxidase in phospholipid vesicles. , 1982, European journal of biochemistry.

[31]  Hartmut Michel,et al.  Structure at 2.8 Å resolution of cytochrome c oxidase from Paracoccus denitrificans , 1995, Nature.

[32]  B. Kadenbach,et al.  Tissue-specific regulation of bovine heart cytochrome-c oxidase activity by ADP via interaction with subunit VIa. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[33]  L. Arend,et al.  Adenosine receptor-mediated calcium mobilization in cortical collecting tubule cells. , 1988, The American journal of physiology.

[34]  P. Mitchell.  CHEMIOSMOTIC COUPLING IN OXIDATIVE AND PHOTOSYNTHETIC PHOSPHORYLATION , 1966, Biological reviews of the Cambridge Philosophical Society.

[35]  E. Margoliash,et al.  Correlation of the kinetics of electron transfer activity of various eukaryotic cytochromes c with binding to mitochondrial cytochrome c oxidase. , 1976, The Journal of biological chemistry.

[36]  B. Kadenbach,et al.  Cross reactivity of monoclonal antibodies and cDNA hybridization suggest evolutionary relationships between cytochrome c oxidase subunits VIa and VIc and between VIIa and VIIb. , 1991, European journal of biochemistry.

[37]  D. Craig,et al.  Studies of 8-azido-ATP adducts reveal two mechanisms by which ATP binding to cytochrome c could inhibit respiration. , 1995, Biochemistry.

[38]  B. Kadenbach,et al.  Regulation of the H+/e− stoichiometry of cytochrome c oxidase from bovine heart by intramitochondrial ATP/ADP ratios , 1996, FEBS letters.

[39]  W. H. Pearlman.  Book Review:Les Oestrogenes Naturels: Biosynthese et Metabolisme. Lise Cedard , 1966 .

[40]  J. Berden,et al.  Anions induce conformational changes and influence the activity and photoaffinity-labelling by 8-azido-ATP of isolated cytochrome c oxidase. , 1988, The Biochemical journal.