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

2019 ◽  
Vol 114 ◽  
pp. 103226 ◽  
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 ◽  
Oxidase Activity ◽  
Flight Muscle ◽  
Allosteric Regulation ◽  
Glycerol Phosphate

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 Evolutionary GEM: Evolution of Cytochrome c Oxidase IV Regulation in Mammals

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Joseph Brockman ◽  
Patricia M. Gray
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Hypoxia Inducible Factor ◽  
Aerobic Bacteria ◽  
Oxygen Species ◽  
Independent Manner ◽  
Hypoxia Inducible Factor 1 ◽  
Early Atmosphere ◽  
Responsive Element ◽  
Multicellular Organisms

Aerobic respiration, although metabolically advantageous in O2-rich environments, can be detrimental to the cell when O2 is not fully reduced resulting in cytotoxic reactive oxygen species (ROS) production. Cytochrome c oxidase subunit 4 (COX-4) is primarily responsible for fully reducing O2 during metabolism and exists as COX4-1 and COX4-2 isoforms. The former exists in normoxia, but is replaced by the latter in hypoxia. This change is brought about by two mechanisms, the first involving regulation by hypoxia inducible factor 1 (HIF-1), which directly upregulates COX4-2 and indirectly degrades COX4-1. The second mechanism involves an oxygen responsive element (ORE), which upregulates COX4-2 in a HIF-1 independent manner. The convergence of two unrelated pathways to regulate COX4-1 and COX4-2 would allow cells to optimize their metabolic profile within an environment experiencing varying O2, such as Earth’s early atmosphere in the case of primitive aerobic bacteria or in multicellular organisms where O2 levels vary between tissues such as lung tissue.

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.

Mitochondrial cytochrome c oxidase and control of energy metabolism: measurements in suspensions of isolated mitochondria

2014 ◽  
Vol 117 (12) ◽  
pp. 1424-1430 ◽  
Author(s):  
David F. Wilson ◽  
David K. Harrison ◽  
Andrei Vinogradov
Keyword(s):  
Oxygen Consumption ◽  
Energy Metabolism ◽  
Cytochrome C ◽  
Oxidative Phosphorylation ◽  
Respiratory Rate ◽  
Cytochrome C Oxidase ◽  
Energy State ◽  
Atp Synthesis ◽  
Oxygen Depletion ◽  
High Energy

Cytochrome c oxidase is the enzyme responsible for oxygen consumption by mitochondrial oxidative phosphorylation and coupling site 3 of oxidative phosphorylation. In this role it determines the cellular rate of ATP synthesis by oxidative phosphorylation and is the key to understanding how energy metabolism is regulated. Four electrons are required for the reduction of oxygen to water, and these are provided by the one-electron donor, cytochrome c. The rate of oxygen consumption (ATP synthesis) is dependent on the fraction of cytochrome c reduced (fred), oxygen pressure (pO2), energy state ([ATP]/[ADP][Pi]), and pH. In coupled mitochondria (high energy state) and pO2 >60 torr, the rate increases in an exponential-like fashion with increasing fred. When the dependence on fred is fitted to the equation rate = a(fred)b, a decreased from 100 to near 20, and b increased from 1.3 to 4 as the pH of the medium increased from 6.5 to 8.3. During oxygen depletion from the medium fred progressively increases and the rate of respiration decreases. The respiratory rate falls to ½ (P50) by about 1.5 torr, at which point fred is substantially increased. The metabolically relevant dependence on pO2 is obtained by correcting for the increase in fred, in which case the P50 is 12 torr. Adding an uncoupler of oxidative phosphorylation eliminates the dependence of the cytochrome c oxidase activity on pH and energy state. The respiratory rate becomes proportional to fred and the P50 decreases to less than 1 torr.

scholarly journals A Cardiac Mitochondrial FGFR1 Mediates the Antithetical Effects of FGF2 Isoforms on Permeability Transition

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2735
Author(s):  
Wattamon Srisakuldee ◽  
Barbara E. Nickel ◽  
Robert R. Fandrich ◽  
Feixong Zhang ◽  
Kishore B. S. Pasumarthi ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Cytochrome C ◽  
Neutralizing Antibodies ◽  
Energy Demand ◽  
Mitochondrial Permeability Transition ◽  
Mitochondrial Protein ◽  
Permeability Transition ◽  
High Energy ◽  
Cytochrome C Release ◽  
Mptp Opening

Mitochondria, abundant organelles in high energy demand cells such as cardiomyocytes, can determine cell death or survival by regulating the opening of mitochondrial permeability transition pore, mPTP. We addressed the hypothesis that the growth factor FGF2, known to reside in intracellular locations, can directly influence mitochondrial susceptibility to mPTP opening. Rat cardiac subsarcolemmal (SSM) or interfibrillar (IFM) mitochondrial suspensions exposed directly to rat 18 kDa low molecular weight (Lo-) FGF2 isoform displayed increased resistance to calcium overload-induced mPTP, measured spectrophotometrically as “swelling”, or as cytochrome c release from mitochondria. Inhibition of mitochondrial protein kinase C epsilon abrogated direct Lo-FGF2 mito-protection. Exposure to the rat 23 kDa high molecular weight (Hi) FGF2 isoform promoted cytochrome c release from SSM and IFM under nonstressed conditions. The effect of Hi-FGF2 was prevented by mPTP inhibitors, pre-exposure to Lo-FGF2, and okadaic acid, a serine/threonine phosphatase inhibitor. Western blotting and immunoelectron microscopy pointed to the presence of immunoreactive FGFR1 in cardiac mitochondria in situ. The direct mito-protective effect of Lo-FGF2, as well as the deleterious effect of Hi-FGF2, were prevented by FGFR1 inhibitors and FGFR1 neutralizing antibodies. We propose that intracellular FGF2 isoforms can modulate mPTP opening by interacting with mito-FGFR1 and relaying isoform-specific intramitochondrial signal transduction.

Protonmotive activity of cytochrome c oxidase: control of oxidoreduction of the heme centers by the protonmotive force in the reconstituted beef heart enzyme

Biochemistry ◽  
1990 ◽  
Vol 29 (12) ◽  
pp. 2939-2945 ◽  
Author(s):  
Nazzareno Capitanio ◽  
Emanuele De Nitto ◽  
Gaetano Villani ◽  
Giuseppe Capitanio ◽  
Sergio Papa
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Protonmotive Force ◽  
Beef Heart

scholarly journals The nature of controlled respiration and its relationship to protonmotive force and proton conductance in blowfly flight-muscle mitochondria

1977 ◽  
Vol 164 (2) ◽  
pp. 305-322 ◽  
Author(s):  
Roger N. Johnson ◽  
Richard G. Hansford
Keyword(s):  
Cytochrome C ◽  
Energy State ◽  
High Energy ◽  
The State ◽  
Protonmotive Force ◽  
Proton Conductance ◽  
Energy Status ◽  
Inner Membrane ◽  
Phosphorylation Potential ◽  
The Difference

1. To determine whether controlled (State 4) pyruvate oxidation can support a high energy state, measurements of the redox span NAD–cytochrome c, phosphorylation potential and protonmotive force (the gradient in electrochemical activity of protons across the mitochondrial inner membrane) were made as indices of energy status. For comparison, these three measurements were also made with glycerol 3-phosphate, an alternative substrate. The two substrates gave essentially identical values for the redox span NAD–cytochrome c in State 4, and the phosphorylation potential was of sufficient magnitude to be considered in equilibrium with the redox span over the first two phosphorylation sites. The magnitude of the protonmotive force in State 4 was much less and the implications of this finding are discussed. 2. Measurements made during the controlled (State 4) to active (State 3) transition indicated that with glycerol 3-phosphate as substrate, both the redox span NAD–cytochrome c and the protonmotive force were diminished; the State 4 → State 3 transition with pyruvate as substrate was accompanied by an increase in the redox span but a decrease in protonmotive force. The contrary behaviour of these two energetic parameters in the presence of pyruvate was ascribed to a transient excess in the flux of protons through the adenosine triphosphatase relative to the protonpumping respiratory chain, in spite of the increased dehydrogenase activity. 3. The lower protonmotive force seen in State 3 relative to State 4 with pyruvate as substrate was due to a diminution of both the electrical (ΔΨ) and the chemical (ΔpH) components; with glycerol 3-phosphate, the magnitude of the decrease in protonmotive force during the State 4 → State 3 transition was similar to that seen with pyruvate, but was due to a large decrease in the electrical component (ΔΨ) and a small rise in the chemical component (ΔpH). The reason for the difference seen in the behaviour of the components of the protonmotive force was investigated but not established. 4. In the presence of oligomycin and ADP, oxidation of pyruvate, but not of glycerol 3-phosphate, supported a greater protonmotive force than in State 4, in keeping with the dehydrogenase activation and increased redox span NAD–cytochrome c found under these conditions. 5. Experiments involving the use of uncoupling agent to stimulate respiration are compared with those in which limiting concentrations of ADP were used. Estimates of the proton conductance of the inner membrane indicate a similar non-linear dependence on uncoupler concentration with the two substrates. 6. A model is proposed as an explanation of the high rates of controlled glycerol 3-phosphate oxidation. The model relies on a high permeability of the inner membrane to protons and other ions being induced by glycerol 3-phosphate oxidation in State 4.

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