scholarly journals Cytochrome c Oxidase at Full Thrust: Regulation and Biological Consequences to Flying Insects

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 470
Author(s):  
Rafael Mesquita ◽  
Alessandro Gaviraghi ◽  
Renata Gonçalves ◽  
Marcos Vannier-Santos ◽  
Julio Mignaco ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Energy Demand ◽  
Redox Balance ◽  
Mitochondrial Enzymes ◽  
Mitochondrial Energy Metabolism ◽  
Atp Production ◽  
Insect Biology ◽  
Oxidant Production ◽  
Atp Supply

Flight dispersal represents a key aspect of the evolutionary and ecological success of insects, allowing escape from predators, mating, and colonization of new niches. The huge energy demand posed by flight activity is essentially met by oxidative phosphorylation (OXPHOS) in flight muscle mitochondria. In insects, mitochondrial ATP supply and oxidant production are regulated by several factors, including the energy demand exerted by changes in adenylate balance. Indeed, adenylate directly regulates OXPHOS by targeting both chemiosmotic ATP production and the activities of specific mitochondrial enzymes. In several organisms, cytochrome c oxidase (COX) is regulated at transcriptional, post-translational, and allosteric levels, impacting mitochondrial energy metabolism, and redox balance. This review will present the concepts on how COX function contributes to flying insect biology, focusing on the existing examples in the literature where its structure and activity are regulated not only by physiological and environmental factors but also how changes in its activity impacts insect biology. We also performed in silico sequence analyses and determined the structure models of three COX subunits (IV, VIa, and VIc) from different insect species to compare with mammalian orthologs. We observed that the sequences and structure models of COXIV, COXVIa, and COXVIc were quite similar to their mammalian counterparts. Remarkably, specific substitutions to phosphomimetic amino acids at critical phosphorylation sites emerge as hallmarks on insect COX sequences, suggesting a new regulatory mechanism of COX activity. Therefore, by providing a physiological and bioenergetic framework of COX regulation in such metabolically extreme models, we hope to expand the knowledge of this critical enzyme complex and the potential consequences for insect dispersal.

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.

Cellular energy utilization and supply during hypoxia in embryonic cardiac myocytes

1996 ◽  
Vol 270 (1) ◽  
pp. L44-L53 ◽  
Author(s):  
G. R. Budinger ◽  
N. Chandel ◽  
Z. H. Shao ◽  
C. Q. Li ◽  
A. Melmed ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Cardiac Myocytes ◽  
Energy Demand ◽  
Adenine Nucleotide ◽  
Energy Utilization ◽  
Embryonic Chick ◽  
O2 Uptake ◽  
Progressive Hypoxia ◽  
Cellular Hypoxia

Studies of intact hearts suggest that cardiac myocytes may have the ability to reversibly suppress metabolic activity and energy demand in states of regional hypoperfusion. However, an ability to suppress respiration in response to hypoxia has never been demonstrated in isolated myocytes. To test this, isolated embryonic chick cardiac myocytes were exposed to progressive hypoxia while their rate of O2 uptake and concentrations of lactate, ATP, ADP, AMP, and phosphocreatine were measured. Compared with the value obtained at an oxygen tension (PO2) of 120 Torr, cellular O2 uptake decreased by 28 +/- 14% (SD) at PO2 = 50 Torr and by 64 +/- 25% at PO2 = 20 Torr (P < 0.05). This decrease was similar after 1 min or 2 h of hypoxia, was sustained for 16 h, and was completely reversible within 2 min after reoxygenation. The reduction in O2 uptake was associated with a decrease in the rate of ATP turnover, but no change in adenine nucleotide or phosphocreatine concentrations. In myocytes adherent to glass cover-slips, O2 uptake and contractile motion were decreased after 30-60 min at 50 and 20 Torr, compared with normoxic values. O2 uptake also was significantly decreased at 50 and 20 Torr in myocytes incubated with N,N,N',N'-tetramethyl-p-phenylenediamine, which suggests that the catalytic activity of cytochrome-c oxidase was partially inhibited during hypoxia. In summary, these results demonstrate that embryonic chick cardiac myocytes can suppress their rates of ATP demand, ATP utilization, and O2 uptake during moderate hypoxia through a mechanism that involves a reversible inhibition of cytochrome-c oxidase. This mechanism may represent a protective response to cellular hypoxia.

scholarly journals Advanced Glycation End Products Inhibit Glucose-Stimulated Insulin Secretion through Nitric Oxide-Dependent Inhibition of Cytochrome c Oxidase and Adenosine Triphosphate Synthesis

Endocrinology ◽  
2009 ◽  
Vol 150 (6) ◽  
pp. 2569-2576 ◽  
Author(s):  
Zhengshan Zhao ◽  
Chunying Zhao ◽  
Xu Hannah Zhang ◽  
Feng Zheng ◽  
Weijing Cai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Secretion ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Atp Production ◽  
Glycation End Products ◽  
End Products ◽  
Glucose Stimulated Insulin Secretion

Advanced glycation end products (AGEs) are implicated in diabetic complications. However, their role in β-cell dysfunction is less clear. In this study we examined the effects of AGEs on islet function in mice and in isolated islets. AGE-BSA or BSA was administered ip to normal mice twice a day for 2 wk. We showed that AGE-BSA-treated mice exhibited significantly higher glucose levels and lower insulin levels in response to glucose challenge than did BSA-treated mice, although there were no significant differences in insulin sensitivity and islet morphology between two groups. Glucose-stimulated insulin secretion by islets of the AGE-BSA-treated mice or AGE-BSA-treated normal islets was significantly lower than that by islets isolated from the BSA-treated mice or BSA-treated normal islets. Furthermore, AGE treatment of islet β-cells inhibited ATP production, and glimepiride, a sulfonylurea derivative, restored glucose-stimulated insulin secretion. Further investigation indicated that AGEs inhibited cytochrome c oxidase activity by inducing the expression of inducible nitric oxide synthase (iNOS). Blocking the formation of nitric oxide with an iNOS selective inhibitor aminoguanidine reversed the inhibitory effects of AGEs on ATP production and insulin secretion. We conclude that AGEs inhibit cytochrome c oxidase and ATP production, leading to the impairment of glucose-stimulated insulin secretion through iNOS-dependent nitric oxide production.

scholarly journals Mitochondrial glycerol phosphate oxidation is modulated by adenylates through allosteric regulation of cytochrome c oxidase activity in mosquito flight muscle

2019 ◽  
Author(s):  
Alessandro Gaviraghi ◽  
Juliana B.R. Correa Soares ◽  
Julio A. Mignaco ◽  
Carlos Frederico L. Fontes ◽  
Marcus F. Oliveira
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Energy Demand ◽  
Flight Muscle ◽  
Allosteric Regulation ◽  
High Energy ◽  
Protonmotive Force ◽  
Independent Manner ◽  
Oxidoreductase Activity ◽  
Regulatory Effects

AbstractThe huge energy demand posed by insect flight activity is met by an efficient oxidative phosphorylation process that takes place within flight muscle mitochondria. In the major arbovirus vector Aedes aegypti, mitochondrial oxidation of pyruvate, proline and glycerol 3 phosphate (G3P) represent the major energy sources of ATP to sustain flight muscle energy demand. Although adenylates exert critical regulatory effects on several mitochondrial enzyme activities, the potential consequences of altered adenylate levels to G3P oxidation remains to be determined. Here, we report that mitochondrial G3P oxidation is controlled by adenylates through allosteric regulation of cytochrome c oxidase (COX) activity in A. aegypti flight muscle. We observed that ADP significantly activated respiratory rates linked to G3P oxidation, in a protonmotive force-independent manner. Kinetic analyses revealed that ADP activates respiration through a slightly cooperative mechanism. Despite adenylates caused no effects on G3P-cytochrome c oxidoreductase activity, COX activity was allosterically activated by ADP. Conversely, ATP exerted powerful inhibitory effects on respiratory rates linked to G3P oxidation and on COX activity. We also observed that high energy phosphate recycling mechanisms did not contribute to the regulatory effects of adenylates on COX activity or G3P oxidation. We conclude that mitochondrial G3P oxidation by A. aegypti flight muscle is regulated by adenylates essentially through the allosteric modulation of COX activity, underscoring the bioenergetic relevance of this novel mechanism and the potential consequences for mosquito dispersal.

scholarly journals Cytochrome C Oxidase Subunit 4 (COX4): A Potential Therapeutic Target for the Treatment of Medullary Thyroid Cancer

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2548
Author(s):  
Athanasios Bikas ◽  
Kirk Jensen ◽  
Aneeta Patel ◽  
John Costello ◽  
Sarah Reynolds ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Cell Lines ◽  
Cancer Progression ◽  
Mitochondrial Respiration ◽  
Thyroid Tissue ◽  
Human Thyroid ◽  
Atp Production ◽  
Tt Cells

The nuclear-encoded subunit 4 of cytochrome c oxidase (COX4) plays a role in regulation of oxidative phosphorylation and contributes to cancer progression. We sought to determine the role of COX4 in differentiated (DTC) and medullary (MTC) thyroid cancers. We examined the expression of COX4 in human thyroid tumors by immunostaining and used shRNA-mediated knockdown of COX4 to evaluate its functional contributions in thyroid cancer cell lines. In human thyroid tissue, the expression of COX4 was higher in cancers than in either normal thyroid (p = 0.0001) or adenomas (p = 0.001). The level of COX4 expression correlated with tumor size (p = 0.04) and lymph-node metastases (p = 0.024) in patients with MTCs. COX4 silencing had no effects on cell signaling activation and mitochondrial respiration in DTC cell lines (FTC133 and BCPAP). In MTC-derived TT cells, COX4 silencing inhibited p70S6K/pS6 and p-ERK signaling, and was associated with decreased oxygen consumption and ATP production. Treatment with potassium cyanide had minimal effects on FTC133 and BCPAP, but inhibited mitochondrial respiration and induced apoptosis in MTC-derived TT cells. Our data demonstrated that metastatic MTCs are characterized by increased expression of COX4, and MTC-derived TT cells are vulnerable to COX4 silencing. These data suggest that COX4 can be considered as a novel molecular target for the treatment of MTC.

Sulphide oxidation and oxidative phosphorylation in the mitochondria of the lugworm

1997 ◽  
Vol 200 (1) ◽  
pp. 83-92 ◽  
Author(s):  
S Vökel ◽  
M K Grieshaber
Keyword(s):  
Oxygen Consumption ◽  
Cytochrome C ◽  
Oxidative Phosphorylation ◽  
Cytochrome C Oxidase ◽  
Electron Flow ◽  
Respiratory Control ◽  
Sulphide Oxidation ◽  
Atp Production ◽  
Sulphide Concentration ◽  
Flow Through

Oxygen consumption, ATP production and cytochrome c oxidase activity of isolated mitochondria from body-wall tissue of Arenicola marina were measured as a function of sulphide concentration, and the effect of inhibitors of the respiratory complexes on these processes was determined. Concentrations of sulphide between 6 and 9 &micro;mol l-1 induced oxygen consumption with a respiratory control ratio of 1.7. Production of ATP was stimulated by the addition of sulphide, reaching a maximal value of 67 nmol min-1 mg-1 protein at a sulphide concentration of 8 &micro;mol l-1. Under these conditions, 1 mole of ATP was formed per mole of sulphide consumed. Higher concentrations of sulphide led to a decrease in ATP production until complete inhibition occurred at approximately 50 &micro;mol l-1. The production of ATP with malate and succinate was stimulated by approximately 15 % in the presence of 4 &micro;mol l-1 sulphide, but decreased at sulphide concentrations higher than 15&shy;20 &micro;mol l-1. Cytochrome c oxidase was also inhibited by sulphide, showing half-maximal inhibition at 1.5 &micro;mol l-1 sulphide. Sulphide-induced ATP production was inhibited by antimycin, cyanide and oligomycin but not by rotenone or salicylhydroxamic acid. The present data indicate that sulphide oxidation is coupled to oxidative phosphorylation solely by electron flow through cytochrome c oxidase, whereas the alternative oxidase does not serve as a coupling site. At sulphide concentrations higher than 20 &micro;mol l-1, oxidation of sulphide serves mainly as a detoxification process rather than as a source of energy.

Alteration of structure and function of ATP synthase and cytochrome c oxidase by lack of Fo-a and Cox3 subunits caused by mitochondrial DNA 9205delTA mutation

2015 ◽  
Vol 466 (3) ◽  
pp. 601-611 ◽  
Author(s):  
Kateřina Hejzlarová ◽  
Vilma Kaplanová ◽  
Hana Nůsková ◽  
Nikola Kovářová ◽  
Pavel Ješina ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Atp Synthase ◽  
Stop Codon ◽  
Threshold Effect ◽  
Structure And Function ◽  
Missense Mutations ◽  
Atp Production ◽  
Atp6 Gene ◽  
And Function

Mutations in the MT-ATP6 gene are frequent causes of severe mitochondrial disorders. Typically, these are missense mutations, but another type is represented by the 9205delTA microdeletion, which removes the stop codon of the MT-ATP6 gene and affects the cleavage site in the MT-ATP8/MT-ATP6/MT-CO3 polycistronic transcript. This interferes with the processing of mRNAs for the Atp6 (Fo-a) subunit of ATP synthase and the Cox3 subunit of cytochrome c oxidase (COX). Two cases described so far presented with strikingly different clinical phenotypes–mild transient lactic acidosis or fatal encephalopathy. To gain more insight into the pathogenic mechanism, we prepared 9205delTA cybrids with mutation load ranging between 52 and 99% and investigated changes in the structure and function of ATP synthase and the COX. We found that 9205delTA mutation strongly reduces the levels of both Fo-a and Cox3 proteins. Lack of Fo-a alters the structure but not the content of ATP synthase, which assembles into a labile, ∼60 kDa smaller, complex retaining ATP hydrolytic activity but which is unable to synthesize ATP. In contrast, lack of Cox3 limits the biosynthesis of COX but does not alter the structure of the enzyme. Consequently, the diminished mitochondrial content of COX and non-functional ATP synthase prevent most mitochondrial ATP production. The biochemical effects caused by the 9205delTA microdeletion displayed a pronounced threshold effect above ∼90% mutation heteroplasmy. We observed a linear relationship between the decrease in subunit Fo-a or Cox3 content and the functional presentation of the defect. Therefore we conclude that the threshold effect originated from a gene–protein level.

scholarly journals Antioxidant activity of tetra nitrosyl iron complex with thiosulfate ligands and its effect on catalytic activity of mitochondrial enzymes in vitro

2019 ◽  
Vol 488 (5) ◽  
pp. 571-575
Author(s):  
I. I. Faingold ◽  
R. A. Kotelnikova ◽  
A. V. Smolina ◽  
D. A. Poletaeva ◽  
Yu. V. Soldatova ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Cytochrome C ◽  
Monoamine Oxidase ◽  
Cytochrome C Oxidase ◽  
Iron Complex ◽  
Monoamine Oxidase A ◽  
Mitochondrial Enzymes ◽  
Nitrosyl Iron Complex ◽  
First Time

The antioxidant and antiradical properties of the tetra nitrosyl iron complex with thiosulfate ligands (TNIC) in the mouse brain homogenates in vitro were also studied. It was found for the first time that TNIC is an effective antioxidant. The effect of TNIC on the catalytic activity of mitochondrial enzymes: cytochrome c oxidase and monoamine oxidase A has been studied. It was shown for the first time that TNIC is an inhibitor of the catalytic activity of cytochrome c oxidase and monoamine oxidase A in the brain mitochondria isolated from animals in vitro.

Oxidation and reduction of cytochrome c by mitochondrial enzymes of Setaria cervi

1995 ◽  
Vol 69 (1) ◽  
pp. 13-17 ◽  
Author(s):  
N. Goyal ◽  
V.M.L. Srivastava
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Potassium Cyanide ◽  
Pyridine Nucleotide ◽  
The Other ◽  
Mitochondrial Enzymes ◽  
Antimycin A ◽  
Setaria Cervi ◽  
Salicylhydroxamic Acid ◽  
Definite Correlation

AbstractA mitochondria-rich fraction isolated from the cuticle-hypodermis-muscie system of Setaria cervi, a bovine filarial parasite, possessed substrate-coupled cytochrome c reductases and cytochrome c oxidase in appreciable activities. All these activities were located predominantly in the membranes. NADH-coupled cytochrome c reductase was more prominent than NADPH- and succinate-coupled reductases. All the three reductases exhibited marked sensitivity to rotenone and antimycin A. Salicylhydroxamic acid strongly inhibited succinate requiring reductase and cytochrome c oxidase, but the other two reductases only mildly. Sodium azide activated the reductases but substantially inhibited the oxidase activity. Potassium cyanide activated the succinate requiring reductase but did not cause any noticeable change in the activities of pyridine nucleotide linked reductases. Anthelmintics also influenced these activities but no definite correlation could be drawn regarding their mode of action.

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