Cytochrome oxidase assembly

Formation of subunits by limited proteolysis of precursor proteins Proteinase cuts precursor protein Mitochondrion Assembly of cytochrome oxidase from cytosolic precursor protein and mitochondrial subunits Restriction of proteolysis to site of cytochrome oxidase assembly... 

Cobalt B Enzymes Coenzymes Cytochrome Oxidase Iron Heme Proteins Electron Transport Iron Proteins with Dinuclear Active Sites Iron Proteins with Mononuclear Active Sites Iron-Sulfur Models of Protein Active Sites Metallocenter Biosynthesis Assembly. Metalloregulation Molybdenum MPT-containing Enzymes Nickel Enzymes Cofactors Nitrogenase Catalysis Assembly Photosynthesis Tungsten Proteins Vanadium in Biology Zinc DNA-binding Proteins. 

Cobalt Inorganic Coordination Chemistry Copper Inorganic Coordination Chemistry Copper Proteins Oxidases Copper Proteins with Dinuclear Active Sites Copper Proteins with Type 2 Sites Cytochrome Oxidase Iron Heme Proteins, Peroxidases, Catalases Catalase-peroxidases Iron Proteins with Mononuclear Active Sites Metal Ion Toxicity Metal-related Diseases of Genetic Origin Metallocenter Biosynthesis Assembly Metalloregulation Peptide Metal Interactions Zinc Enzymes. 

Genetic defects of cytochrome c oxidase assembly. Physiol. Res. 2004 53 213-223. 34. 

The last of the three proton-pumping assemblies of the respiratory chain is cytochrome c oxidase (Complex IV). Cytochrome oxidase catalyzes the transfer of electrons from the reduced form of cytochrome c to molecular oxygen, the final acceptor. 

Figure 3-32. (B) The assembly of an electroswitchable, electrically-contacted electrode for the bioelectrocatalyzed reduction of O2 consisting of a crosslinked affinity complex of cytochrome c/cytochrome oxidase (cyt c/COx) on a polyacrylic acid-polyethylene imine film that includes incorporated Cu -ions. The conductivity of the film and the electrical contacting of the redox-proteins is accomphshed by applying a potential of -0.5 V vs. SCE and the generation of Cu-clusters in the film. Reproduced with permission from ref. 89. Copyright 2003 American Chemical Society.

Cooperative Interaction between Mitochondrial and Nuclear Genomes Cytochrome c Oxidase Assembly as a Model... 

Rubin, M.S., Tzagoloff, A. Assembly of the mitochondrial membrane system, X. Mitochondrial synthesis of three of the subunit proteins of yeast cytochrome oxidase. J. biol. Chem. 248, 4275-4279 (1973)... 

OXPHOS, oxidative phosphorylation NDUF, nuclear-encoded subunits of human complex I Fp, flavoprotein ANT, adenine nucleotide translocase SCO, synthesis of cytochrome c oxidase (assembly gene) COX, cytochrome c oxidase. 

In addition to these heaAry mitochondria, the exclusive carriers of cytochrome oxidase, de Duve distinguishes light mitochondria or lysosomes , which contain alkaline phosphatase, ribonudease, desoxy-ribonudease, cathepsin (i.e. the complete assembly of intracellular peptidases), and most of the )3-glucuronidase. In these intact partides, these hydrolases do not have access to their substrates when the latter are situated in the medium around the partides. 

Yeast cytochrome oxidase is built up from seven different subunits, of which four are synthesized in the cytosol, and three in the mitochondria (25). R. 0. Poyton (26) recently reported evidence suggesting that the four cytosolic subunits are synthesized in one peptide chain. This precursor protein might be split by limited proteolysis in connection with or after transport from the cytosol to the inner mitochondrial membrane. Here seems to be an example of a proteolytic process in yeast participating in subcellular translocation of subunits and assembly of an enzyme (see Table V). V/hich proteinase is involved in this process, and whether specific inhibitors also play a part, is as present unknown. 

Leary, S.C., Cobine, P.A., Kaufinan, B.A., Gueicin, G.H., Mattman, A., Palaty, J., Lockitch, G., Winge, D.R., Rustin, P, Horvath, R., and Shoubridge, E.A. (2007). The human cytochrome c oxidase assembly factors SCOl and SC02 have regulatory roles in the maintenance of cellular copper homeostasis. Cell Metab. 5,9-20. 

The half lives and the pool sizes of the precursor polypeptides were derived from the time courses of labeling shown in Fig. 9. They are summarized in Table II. As can be seen, the precursor pool of the 20,000 Mr subunit of cytochrome oxidase is relatively small compared to the precursor pools of the other cytochrome oxidase subunits. This 20,000 Mr subunit was shown to be produced by the chloramphenicol-sensitive mitochondrial protein synthesis (Fig. 7B). Consequently, soon after the addition of chloramphenicol, the precursor pool of this subunit is exhausted, making a further assembly of the holoenzyme impossible. This explains why, after... 

The data of Table II provide additional information about the subunits. The precursor pool sizes of the three mitochondrially synthesized cytochrome oxidase subunits differ markedly, being 2% for the 20,000 Mr subunit, 5% for the 28,000 Mr subunit, and 10% for the 36,000 Mr subunit. Hence, in the presence of cycloheximide, the assembly of cytochrome oxidase continues only for a limited period of time, i.e., until the smallest cytoplasmic precursor pool is exhausted. The amount of label which appears in the holoenzyme after this period of time decreases as the size of the precursor pool to be passed increases. This fact explains why in the presence of cycloheximide, less radioactivity appeared in the 28,000 Mr and 36,000 Mr subunits than in the 20,000 Mr subunit (Fig. 7B). However, when cycloheximide is removed, the assembly of the holoenzyme recommences, and all of the H-labeled polypeptides can be integrated. In this manner, a higher cycloheximide-resistant radioactive labeling of the 28,000 Mr and the 36,000 Mr subunits of cytochrome oxidase is obtained with N. crassa. ... 

There is now considerable evidence indicating a close interdependence between cytoplasmic- and mitoribosomal-directed proteins for the assembly and function of inner-membrane complexes like cytochrome oxidase and the oligomycin-sensitive ATPase. Thus an alteration in a nuclear gene product could profoundly affect the level or functioning of a mitochondrial translation product or products such a situation could apply as well to the replication of wild-type mtDNA. 

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