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Clinical Science (London, England :... Mar 2016As with other mitochondrial respiratory chain components, marked clinical and genetic heterogeneity is observed in patients with a cytochrome c oxidase deficiency. This... (Review)
Review
As with other mitochondrial respiratory chain components, marked clinical and genetic heterogeneity is observed in patients with a cytochrome c oxidase deficiency. This constitutes a considerable diagnostic challenge and raises a number of puzzling questions. So far, pathological mutations have been reported in more than 30 genes, in both mitochondrial and nuclear DNA, affecting either structural subunits of the enzyme or proteins involved in its biogenesis. In this review, we discuss the possible causes of the discrepancy between the spectacular advances made in the identification of the molecular bases of cytochrome oxidase deficiency and the lack of any efficient treatment in diseases resulting from such deficiencies. This brings back many unsolved questions related to the frequent delay of clinical manifestation, variable course and severity, and tissue-involvement often associated with these diseases. In this context, we stress the importance of studying different models of these diseases, but also discuss the limitations encountered in most available disease models. In the future, with the possible exception of replacement therapy using genes, cells or organs, a better understanding of underlying mechanism(s) of these mitochondrial diseases is presumably required to develop efficient therapy.
Topics: Animals; Cells, Cultured; Cytochrome-c Oxidase Deficiency; Disease Models, Animal; Electron Transport Complex IV; Humans; Molecular Structure
PubMed: 26846578
DOI: 10.1042/CS20150707 -
Brain Structure & Function Dec 2021An ordered relation of structure and function has been a cornerstone in thinking about brain organization. Like the brain itself, however, this is not straightforward... (Review)
Review
An ordered relation of structure and function has been a cornerstone in thinking about brain organization. Like the brain itself, however, this is not straightforward and is confounded both by functional intricacy and structural plasticity (many routes to a given outcome). As a striking case of putative structure-function correlation, this mini-review focuses on the relatively well-characterized pattern of cytochrome oxidase (CO) blobs (aka "patches" or "puffs") in the supragranular layers of macaque monkey visual cortex. The pattern is without doubt visually compelling, and the semi-dichotomous array of CO+ blobs and CO- interblobs is consistent with multiple studies reporting compartment-specific preferential connectivity and distinctive physiological response properties. Nevertheless, as briefly reviewed here, the finer anatomical organization of this system is surprisingly under-investigated, and the relation to functional aspects, therefore, unclear. Microcircuitry, cell type, and three-dimensional spatiotemporal level investigations of the CO+ CO- pattern are needed and may open new views to structure-function organization of visual cortex, and to phylogenetic and ontogenetic comparisons across nonhuman primates (NHP), and between NHP and humans.
Topics: Animals; Electron Transport Complex IV; Macaca; Phylogeny; Visual Cortex
PubMed: 34382115
DOI: 10.1007/s00429-021-02360-2 -
Cytochrome c oxidase: Intermediates of the catalytic cycle and their energy-coupled interconversion.FEBS Letters Mar 2012Several issues relevant to the current studies of cytochrome c oxidase catalytic mechanism are discussed. The following points are raised. (1) The terminology currently... (Review)
Review
Several issues relevant to the current studies of cytochrome c oxidase catalytic mechanism are discussed. The following points are raised. (1) The terminology currently used to describe the catalytic cycle of cytochrome oxidase is outdated and rather confusing. Presumably, it would be revised so as to share nomenclature of the intermediates with other oxygen-reactive heme enzymes like P450 or peroxidases. (2) A "catalytic cycle" of cytochrome oxidase involving complete reduction of the enzyme by 4 electrons followed by oxidation by O(2) is a chimera composed artificially from two partial reactions, reductive and oxidative phases, that never operate together as a true multi-turnover catalytic cycle. The 4e(-) reduction-oxidation cycle would not serve a paradigm for oxygen reduction mechanism and protonmotive function of cytochrome oxidase. (3) The foremost role of the K-proton channel in the catalytic cycle may consist in securing faultless delivery of protons for heterolytic O-O bond cleavage in the oxygen-reducing site, minimizing the danger of homolytic scission reaction route. (4) Protonmotive mechanism of cytochrome oxidase may vary notably for the different single-electron steps in the catalytic cycle.
Topics: Animals; Bacterial Proteins; Biocatalysis; Cattle; Electron Transport; Electron Transport Complex IV; Energy Metabolism; Models, Biological; Models, Chemical; Oxidation-Reduction; Rhodobacter sphaeroides
PubMed: 21889506
DOI: 10.1016/j.febslet.2011.08.037 -
Biochimica Et Biophysica Acta.... Dec 2020This review examines the current state of the art on the evolution of the families of Heme Copper Oxygen reductases (HCO) that oxidize cytochrome c and reduce oxygen to... (Review)
Review
This review examines the current state of the art on the evolution of the families of Heme Copper Oxygen reductases (HCO) that oxidize cytochrome c and reduce oxygen to water, chiefly cytochrome oxidase, COX. COX is present in many bacterial and most eukaryotic lineages, but its origin has remained elusive. After examining previous proposals for COX evolution, the review summarizes recent insights suggesting that COX enzymes might have evolved in soil dwelling, probably iron-oxidizing bacteria which lived on emerged land over two billion years ago. These bacteria were the likely ancestors of extant acidophilic iron-oxidizers such as Acidithiobacillus spp., which belong to basal lineages of the phylum Proteobacteria. Proteobacteria may thus be considered the originators of COX, which was then laterally transferred to other prokaryotes. The taxonomy of bacteria is presented in relation to the current distribution of COX and C family oxidases, from which COX may have evolved.
Topics: Electron Transport Complex IV; Evolution, Molecular; Heme; Multigene Family; Oxygen Consumption; Phylogeny
PubMed: 32890468
DOI: 10.1016/j.bbabio.2020.148304 -
Journal of Biochemistry Jan 2022
Topics: Crystallography; Cytochromes c; Electron Transport Complex IV; Protein Conformation
PubMed: 34697634
DOI: 10.1093/jb/mvab118 -
International Journal of Molecular... Mar 2023The review focuses on recent advances regarding the effects of natural and artificial amphipathic compounds on terminal oxidases. Terminal oxidases are fascinating... (Review)
Review
The review focuses on recent advances regarding the effects of natural and artificial amphipathic compounds on terminal oxidases. Terminal oxidases are fascinating biomolecular devices which couple the oxidation of respiratory substrates with generation of a proton motive force used by the cell for ATP production and other needs. The role of endogenous lipids in the enzyme structure and function is highlighted. The main regularities of the interaction between the most popular detergents and terminal oxidases of various types are described. A hypothesis about the physiological regulation of mitochondrial-type enzymes by lipid-soluble ligands is considered.
Topics: Oxidoreductases; Electron Transport Complex IV; Oxidation-Reduction
PubMed: 37047401
DOI: 10.3390/ijms24076428 -
Philosophical Transactions of the Royal... Jun 1997Cytochrome oxidase is the terminal electron acceptor of the mitochondrial respiratory chain. It is responsible for the vast majority of oxygen consumption in the body... (Review)
Review
Cytochrome oxidase is the terminal electron acceptor of the mitochondrial respiratory chain. It is responsible for the vast majority of oxygen consumption in the body and essential for the efficient generation of cellular ATP. The enzyme contains four redox active metal centres; one of these, the binuclear CuA centre, has a strong absorbance in the near-infrared that enables it to be detectable in vivo by near-infrared spectroscopy. However, the fact that the concentration of this centre is less than 10% of that of haemoglobin means that its detection is not a trivial matter. Unlike the case with deoxyhaemoglobin and oxyhaemoglobin, concentration changes of the total cytochrome oxidase protein occur very slowly (over days) and are therefore not easily detectable by near-infrared spectroscopy. However, the copper centre rapidly accepts and donates an electron, and can thus change its redox state quickly; this redox change is detectable by near-infrared spectroscopy. Many factors can affect the CuA redox state in vivo (Cooper et al. 1994), but most significant is likely to be the molecular oxygen concentration (at low oxygen tensions, electrons build up on CuA as reduction of oxygen by the enzyme starts to limit the steady-state rate of electron transfer). The factors underlying haemoglobin oxygenation, deoxygenation and blood volume changes are, in general, well understood by the clinicians and physiologists who perform near-infrared spectroscopy measurements. In contrast, the factors that control the steady-state redox level of CuA in cytochrome oxidase are still a matter of active debate, even amongst biochemists studying the isolated enzyme and mitochondria. Coupled with the difficulties of accurate in vivo measurements it is perhaps not surprising that the field of cytochrome oxidase near-infrared spectroscopy has a somewhat chequered past. Too often papers have been written with insufficient information to enable the measurements to be repeated and few attempts have been made to test the algorithms in vivo. In recent years a number of research groups and commercial spectrometer manufacturers have made a concerted attempt to not only say how they are attempting to measure cytochrome oxidase by near-infrared spectroscopy but also to demonstrate that they are really doing so. We applaud these attempts, which in general fall into three areas: first, modelling of data can be performed to determine what problems are likely to derail cytochrome oxidase detection algorithms (Matcher et al. 1995); secondly haemoglobin concentration changes can be made by haemodilution (using saline or artificial blood substitutes) in animals (Tamura 1993) or patients (Skov & Greisen 1994); and thirdly, the cytochrome oxidase redox state can be fixed by the use of mitochondrial inhibitors and then attempts make to cause spurious cytochrome changes by dramatically varying haemoglobin oxygenation, haemoglobin concentration and light scattering (Cooper et al. 1997). We have previously written reviews covering the difficulties of measuring the cytochrome near-infrared spectroscopy signal in vivo (Cooper et al. 1997) and the factors affecting the oxidation state of cytochrome oxidase CuA (Cooper et al. 1994). In this article we would like to strike a somewhat more optimistic note--we will stress the usefulness this measurement may have in the clinical environment, as well as describing conditions under which we can have confidence that we are measuring real changes in the CuA redox state.
Topics: Animals; Asphyxia Neonatorum; Electron Transport; Electron Transport Complex IV; Energy Metabolism; Hemoglobins; Humans; Hypoxia; Infant, Newborn; Mitochondria; Oxyhemoglobins; Spectrophotometry, Infrared
PubMed: 9232854
DOI: 10.1098/rstb.1997.0048 -
Biochimica Et Biophysica Acta Apr 2004Cytochrome c is the specific and efficient electron transfer mediator between the two last redox complexes of the mitochondrial respiratory chain. Its interaction with... (Review)
Review
Cytochrome c is the specific and efficient electron transfer mediator between the two last redox complexes of the mitochondrial respiratory chain. Its interaction with both partner proteins, namely cytochrome c(1) (of complex III) and the hydrophilic Cu(A) domain (of subunit II of oxidase), is transient, and known to be guided mainly by electrostatic interactions, with a set of acidic residues on the presumed docking site on the Cu(A) domain surface and a complementary region of opposite charges exposed on cytochrome c. Information from recent structure determinations of oxidases from both mitochondria and bacteria, site-directed mutagenesis approaches, kinetic data obtained from the analysis of isolated soluble modules of interacting redox partners, and computational approaches have yielded new insights into the docking and electron transfer mechanisms. Here, we summarize and discuss recent results obtained from bacterial cytochrome c oxidases from both Paracoccus denitrificans, in which the primary electrostatic encounter most closely matches the mitochondrial situation, and the Thermus thermophilus ba(3) oxidase in which docking and electron transfer is predominantly based on hydrophobic interactions.
Topics: Catalytic Domain; Cytochromes c; Electron Transport; Electron Transport Complex IV; Kinetics; Models, Molecular; Mutagenesis, Site-Directed; Nuclear Magnetic Resonance, Biomolecular; Oxidation-Reduction; Paracoccus denitrificans; Static Electricity; Thermus thermophilus
PubMed: 15100042
DOI: 10.1016/j.bbabio.2003.10.010 -
FEBS Letters Mar 1994The cytochrome bc complex which is encoded by the fixNOPQ operon in Bradyrhizobium japonicum, is the most distant member of the haem-copper cytochrome oxidase family. We... (Review)
Review
The cytochrome bc complex which is encoded by the fixNOPQ operon in Bradyrhizobium japonicum, is the most distant member of the haem-copper cytochrome oxidase family. We have found that its major subunit, FixN, is homologous to the NorB subunit of nitric oxide reductase in a purple bacterium. A second evolutionary link between cytochrome oxidases and denitrification enzymes is the presence of a similar binuclear copper site in cytochrome aa3 (the mitochondrial oxidase) and nitrous oxide reductase. This centre was probably acquired by a primitive FixN-type oxidase, leading to the evolution of the mitochondrial-type oxidase. These links suggest that the oxygen-reducing respiratory chain developed from the anaerobic, denitrifying respiratory system.
Topics: Amino Acid Sequence; Biological Evolution; Copper; Electron Transport Complex IV; Molecular Sequence Data; Nitrites; Oxidoreductases
PubMed: 8137905
DOI: 10.1016/0014-5793(94)80228-9 -
Cells Sep 2020Estradiol, testosterone and other steroid hormones inhibit cytochrome oxidase (CcO) purified from bovine heart. The inhibition is strongly dependent on concentration of...
Estradiol, testosterone and other steroid hormones inhibit cytochrome oxidase (CcO) purified from bovine heart. The inhibition is strongly dependent on concentration of dodecyl-maltoside (DM) in the assay. The plots of K vs [DM] are linear for both estradiol and testosterone which may indicate an 1:1 stoichiometry competition between the hormones and the detergent. Binding of estradiol, but not of testosterone, brings about spectral shift of the oxidized CcO consistent with an effect on heme . We presume that the hormones bind to CcO at the bile acid binding site described by Ferguson-Miller and collaborators. Estradiol is shown to inhibit intraprotein electron transfer between hemes and Notably, neither estradiol nor testosterone suppresses the peroxidase activity of CcO. Such a specific mode of action indicates that inhibition of CcO activity by the hormones is associated with impairing proton transfer via the K-proton channel.
Topics: Animals; Cattle; Cyanides; Electron Transport; Electron Transport Complex IV; Estradiol; Glucosides; Gonadal Steroid Hormones; Heme; Kinetics; Oxidation-Reduction; Testosterone
PubMed: 33003582
DOI: 10.3390/cells9102211