scholarly journals Cytochrome c Oxidase Subunit 4 Isoform Exchange Results in Modulation of Oxygen Affinity

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 443 ◽  
Author(s):  
David Pajuelo Reguera ◽  
Kristýna Čunátová ◽  
Marek Vrbacký ◽  
Alena Pecinová ◽  
Josef Houštěk ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Oxygen Affinity ◽  
Intact Cells ◽  
Knock Out ◽  
Atp Production ◽  
Oxygen Kinetics ◽  
Biochemical Mechanisms

Cytochrome c oxidase (COX) is regulated through tissue-, development- or environment-controlled expression of subunit isoforms. The COX4 subunit is thought to optimize respiratory chain function according to oxygen-controlled expression of its isoforms COX4i1 and COX4i2. However, biochemical mechanisms of regulation by the two variants are only partly understood. We created an HEK293-based knock-out cellular model devoid of both isoforms (COX4i1/2 KO). Subsequent knock-in of COX4i1 or COX4i2 generated cells with exclusive expression of respective isoform. Both isoforms complemented the respiratory defect of COX4i1/2 KO. The content, composition, and incorporation of COX into supercomplexes were comparable in COX4i1- and COX4i2-expressing cells. Also, COX activity, cytochrome c affinity, and respiratory rates were undistinguishable in cells expressing either isoform. Analysis of energy metabolism and the redox state in intact cells uncovered modestly increased preference for mitochondrial ATP production, consistent with the increased NADH pool oxidation and lower ROS in COX4i2-expressing cells in normoxia. Most remarkable changes were uncovered in COX oxygen kinetics. The p50 (partial pressure of oxygen at half-maximal respiration) was increased twofold in COX4i2 versus COX4i1 cells, indicating decreased oxygen affinity of the COX4i2-containing enzyme. Our finding supports the key role of the COX4i2-containing enzyme in hypoxia-sensing pathways of energy metabolism.

Decreased affinity for oxygen of cytochrome-c oxidase in Leigh syndrome caused by SURF1 mutations

2004 ◽  
Vol 287 (5) ◽  
pp. C1384-C1388 ◽  
Author(s):  
Petr Pecina ◽  
Erich Gnaiger ◽  
Jiří Zeman ◽  
Ewa Pronicka ◽  
Josef Houštěk
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Oxygen Affinity ◽  
Leigh Syndrome ◽  
Respiratory Response ◽  
Low Oxygen ◽  
Cultured Fibroblasts ◽  
Oxygen Kinetics ◽  
Coupled Cells

Mutations in the gene SURF1 prevent synthesis of cytochrome- c oxidase (COX)-specific assembly protein and result in a fatal neurological disorder, Leigh syndrome. Because this severe COX deficiency presents with barely detectable changes of cellular respiratory rates under normoxic conditions, we analyzed the respiratory response to low oxygen in cultured fibroblasts harboring SURF1 mutations with high-resolution respirometry. The oxygen kinetics was quantified by the partial pressure of oxygen (Po2) at half-maximal respiration rate (P50) in intact coupled cells and in digitonin-permeabilized uncoupled cells. In both cases, the P50 in patients was elevated 2.1- and 3.3-fold, respectively, indicating decreased affinity of COX for oxygen. These results suggest that at physiologically low intracellular Po2, the depressed oxygen affinity may lead in vivo to limitations of respiration, resulting in impaired energy provision in Leigh syndrome patients.

scholarly journals Mechanical Ventilation Preserves Diaphragm Mitochondrial Function in a Rat Sepsis Model

2020 ◽  
Author(s):  
Pierre Eyenga ◽  
Damien Roussel ◽  
Benjamin Rey ◽  
Patrice Ndille ◽  
Loic Teulier ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Oxygen Consumption ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Oxidase Activity ◽  
Ros Generation ◽  
Mitochondrial Oxygen Consumption ◽  
Atp Production ◽  
Mitochondrial Ros ◽  
Mda Content

Abstract Background: To describe the effect of mechanical ventilation on diaphragm mitochondrial oxygen consumption, ATP production, reactive oxygen species (ROS) generation, and cytochrome-c oxidase activity and content, and their relationship to diaphragm strength in an experimental model of sepsis.Methods: A cecal ligation and puncture (CLP) protocol was performed in 12 rats while 12 controls underwent sham-operation. Half of the rats in each group were paralyzed and mechanically ventilated. We performed blood gas analysis and lactic acid assays 6 hours after surgery. Afterwards, we measured diaphragm strength and mitochondrial oxygen consumption, ATP and ROS generation, and cytochrome-c oxidase activity. We also measured malondialdehyde (MDA) content as an index of lipid peroxidation, and mRNA expression of the pro-inflammatory interleukin-1β (IL-1β) in diaphragms.Results: CLP rats showed severe hypotension, metabolic acidosis, and upregulation of diaphragm IL-1β mRNA expression. Compared to sham controls, spontaneously breathing CLP rats showed lower diaphragm force and increased susceptibility to fatigue, along with depressed mitochondrial oxygen consumption and ATP production and cytochrome-c oxidase activity. These rats also showed increased mitochondrial ROS generation and MDA content. Mechanical ventilation markedly restored mitochondrial oxygen consumption and ATP production in CLP rats; lowered mitochondrial ROS production by the complex 3; and preserved cytochrome-c oxidase activity.Conclusion: In an experimental model of sepsis, early initiation of mechanical ventilation restores diaphragm mitochondrial function.

scholarly journals Role of subunit III and its lipids in the molecular mechanism of cytochrome c oxidase

2015 ◽  
Vol 1847 (8) ◽  
pp. 690-697 ◽  
Author(s):  
Vivek Sharma ◽  
Pauliina Ala-Vannesluoma ◽  
Ilpo Vattulainen ◽  
Mårten Wikström ◽  
Tomasz Róg
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Molecular Mechanism ◽  
Subunit Iii

The structural and functional role of lysine residues in the binding domain of cytochrome c in the electron transfer to cytochrome c oxidase

1999 ◽  
Vol 261 (2) ◽  
pp. 379-391 ◽  
Author(s):  
Susanne Dopner ◽  
Peter Hildebrandt ◽  
Federico I. Rosell ◽  
A. Grant Mauk ◽  
Matthias von Walter ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Functional Role ◽  
Binding Domain ◽  
Lysine Residues

Cox2A/Cox2B subunit interaction in Polytomella sp. cytochrome c oxidase: role of the Cox2B subunit extension

2017 ◽  
Vol 49 (6) ◽  
pp. 453-461 ◽  
Author(s):  
Alejandra Jiménez-Suárez ◽  
Miriam Vázquez-Acevedo ◽  
Héctor Miranda-Astudillo ◽  
Diego González-Halphen
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Subunit Interaction
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