Interaction of Oxidative Phosphorylation and Work in the Heart, In Vivo

Physiology ◽  
1989 ◽  
Vol 4 (6) ◽  
pp. 215-218
Author(s):  
RS Balaban ◽  
FW Heineman
Keyword(s):  
Oxidative Phosphorylation ◽  
Control Mechanism ◽  
Atp Hydrolysis ◽  
Atp Production ◽  
Hydrolysis Products ◽  
The Subject ◽  
Regulatory Sites

The mechanism that balances the rates of myocardial ATP production and use is the subject of this brief review. Recent in vivo data suggest that this control mechanism does not depend solely on the concentrations of ATP hydrolysis products. Other potential regulatory sites are currently being investigated.

Ca2+ activation of heart mitochondrial oxidative phosphorylation: role of the F0/F1-ATPase

2000 ◽  
Vol 278 (2) ◽  
pp. C423-C435 ◽  
Author(s):  
Paul R. Territo ◽  
Vamsi K. Mootha ◽  
Stephanie A. French ◽  
Robert S. Balaban
Keyword(s):  
Oxidative Phosphorylation ◽  
Atp Synthesis ◽  
High Energy ◽  
Ruthenium Red ◽  
Maximal Effect ◽  
Production Rates ◽  
Atp Production ◽  
The Matrix

Ca2+ has been postulated as a cytosolic second messenger in the regulation of cardiac oxidative phosphorylation. This hypothesis draws support from the well-known effects of Ca2+ on muscle activity, which is stimulated in parallel with the Ca2+-sensitive dehydrogenases (CaDH). The effects of Ca2+ on oxidative phosphorylation were further investigated in isolated porcine heart mitochondria at the level of metabolic driving force (NADH or Δψ) and ATP production rates (flow). The resulting force-flow (F-F) relationships permitted the analysis of Ca2+ effects on several putative control points within oxidative phosphorylation, simultaneously. The F-F relationships resulting from additions of carbon substrates alone provided a model of pure CaDH activation. Comparing this curve with variable Ca2+ concentration ([Ca2+]) effects revealed an approximate twofold higher ATP production rate than could be explained by a simple increase in NADH or Δψ via CaDH activation. The half-maximal effect of Ca2+ at state 3 was 157 nM and was completely inhibited by ruthenium red (1 μM), indicating matrix dependence of the Ca2+ effect. Arsenate was used as a probe to differentiate between F0/F1-ATPase and adenylate translocase activity by a futile recycling of ADP-arsenate within the matrix, catalyzed by the F0/F1-ATPase. Ca2+increased the ADP arsenylation rate more than twofold, suggesting a direct effect on the F0/F1-ATPase. These results suggest that Ca2+ activates cardiac aerobic respiration at the level of both the CaDH and F0/F1-ATPase. This type of parallel control of both intermediary metabolism and ATP synthesis may provide a mechanism of altering ATP production rates with minimal changes in the high-energy intermediates as observed in vivo.

scholarly journals Oxidative phosphorylation is required for powering motility and development of the sleeping sickness parasite Trypanosoma brucei within the tsetse fly vector

2021 ◽  
Author(s):  
Caroline E Dewar ◽  
Aitor Casas-Sánchez ◽  
Constentin Dieme ◽  
Aline Crouzols ◽  
Lee Haines ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Trypanosoma Brucei ◽  
Atp Synthase ◽  
Sleeping Sickness ◽  
Tsetse Fly ◽  
Tsetse Flies ◽  
Respiratory Chain Complexes ◽  
Atp Production

The single-celled parasite Trypanosoma brucei causes sleeping sickness in humans and nagana in livestock and is transmitted by hematophagous tsetse flies. Lifecycle progression from mammalian bloodstream form to tsetse midgut form and, subsequently, infective salivary gland form depends on complex developmental steps and migration within different fly tissues. As the parasite colonises the glucose-poor insect midgut, its ATP production is thought to depend on activation of mitochondrial amino acid catabolism via oxidative phosphorylation. This process involves respiratory chain complexes and the F1FO-ATP synthase, and it requires protein subunits of these complexes that are encoded in the parasite's mitochondrial DNA (kinetoplast or kDNA). Here we show that a progressive loss of kDNA-encoded functions correlates with an increasingly impaired ability of T. brucei to initiate and complete its development in the tsetse. First, parasites with a mutated F1FO-ATP synthase with a reduced capacity for oxidative phosphorylation can initiate differentiation from bloodstream to insect form, but they are unable to proliferate in vitro. Unexpectedly, these cells can still colonise the tsetse midgut. However, these parasites exhibit a motility defect and are severely impaired in colonising or migrating to subsequent tsetse tissues. Second, parasites with a fully disrupted F1FO-ATP synthase complex that is completely unable to produce ATP by oxidative phosphorylation can still differentiate to the first insect stage in vitro but die within a few days and cannot establish a midgut infection in vivo. Third, mutant parasites lacking kDNA entirely can initiate differentiation but die within 24 h. Together, these three scenarios show that efficient ATP production via oxidative phosphorylation is not essential for initial colonisation of the tsetse vector, but it is required to power trypanosome migration within the fly.

Maximum oxidative phosphorylation capacity of the mammalian heart

1997 ◽  
Vol 272 (2) ◽  
pp. H769-H775 ◽  
Author(s):  
V. K. Mootha ◽  
A. E. Arai ◽  
R. S. Balaban
Keyword(s):  
Oxidative Phosphorylation ◽  
Oxidative Capacity ◽  
In Vivo Studies ◽  
Production Reserve ◽  
Myocardial Performance ◽  
Atp Production ◽  
Mammalian Heart ◽  
Intact Heart ◽  
Mitochondrial Respiratory

It is difficult to estimate the maximum in vivo aerobic ATP production rate of the intact heart independent of limitations imposed by blood flow, oxygen delivery, and maximum mechanical power. This value is critical for establishing the kinetic parameters that control oxidative phosphorylation, as well as for providing insights into the limits of myocardial performance. In this study, the maximum ADP-P(i)-driven heart mitochondrial respiratory rate (MV(O2 mito)) was determined with saturating levels of oxygen, substrates, and cofactors at 37 degrees C. These rates were normalized to cytochrome alpha1 alpha3 (cytochrome oxidase; Cyt a) content. To extrapolate this rate to the intact heart, the Cyt a content of the myocardium (nmol Cyt a/g wet wt myocardium) was determined in the same hearts. The maximum ADP-P(i)-driven mitochondrial respiratory rates were 676 +/- 31 and 665 +/- 65 nmol O2 x min(-1) x nmol Cyt a(-1) in the dog and pig, respectively. The Cyt a content in the two species was 43.6 +/- 2.4 and 36.6 +/- 3.1 nmol Cyt a/g wet wt, respectively. With these values, the MV(O2 mito) was calculated to be 29.5 (dog) and 24.3 (pig) micromol O2 x min(-1) x g wet wt myocardium(-1). Comparison with in vivo studies shows that the exercising heart can utilize 80-90% of its maximum oxidative capacity, implying there is little aerobic ATP production reserve in the mammalian heart.

Substrate regulation of mitochondrial oxidative phosphorylation in hypercapnic rabbit muscle

1992 ◽  
Vol 72 (2) ◽  
pp. 521-528 ◽  
Author(s):  
S. Nioka ◽  
Z. Argov ◽  
G. P. Dobson ◽  
R. E. Forster ◽  
H. V. Subramanian ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Intracellular Ph ◽  
Isometric Tension ◽  
Muscle Performance ◽  
Oxidative Enzymes ◽  
Rabbit Muscle ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Atp Production

Endurance muscle performance is highly dependent on ATP production from mitochondrial oxidative phosphorylation. To study the role of the mitochondrial oxidative enzymes in muscle fatigue, we analyzed the relationship between the concentrations of substrates associated with ATP synthesis and the muscle performance of electrically stimulated rabbit muscle under CO2-induced acidosis. Two different conditions of pacing-induced muscle performance were produced in the gastrocnemius and soleus muscle groups in anesthetized rabbits by stimulating the sciatic nerve submaximally at two frequencies. Phosphorus nuclear magnetic resonance was used to measure ATP, phosphocreatine, and Pi and to provide data for a calculation of intracellular pH and free ADP. To induce acidosis, the animal was ventilated with 20% CO2. The administration of CO2 effectively reduced the intracellular pH from 6.9 to 6.7 and reduced the isometric tension-time integral (TTI) to below half the value measured in normocapnia at the low pacing frequency. A twofold increase in the pacing frequency resulted in a doubling of the TTI in normocapnia and a tripling of TTI in hypercapnia. The increases in TTI corresponded with increases in free ADP and Pi concentrations. Under the various conditions, all free ADP values were near the in vitro Michaelis-Menten constant (Km) of ADP. The Michaelis-Menten relationship of the oxidative phosphorylative enzymes was applied to the change in substrate concentrations with respect to TTI. From this relationship we observed that the in vivo Km of free ADP was 26 microM, which is close to the in nitro Km, and that Km and maximal reaction velocity did not change under hypercapnia and increased pacing frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals BRAWNIN: A sORF-encoded Peptide Essential for Vertebrate Mitochondrial Complex III Assembly

2020 ◽  
Author(s):  
Shan Zhang ◽  
Chao Liang ◽  
Camille Mary ◽  
Baptiste Kerouanton ◽  
Joel Francisco ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Metabolic Flux ◽  
Chain Complex ◽  
Early Death ◽  
Open Reading Frame ◽  
Complex Iii ◽  
Reading Frame ◽  
Atp Production ◽  
Small Open Reading Frame

AbstractThe emergence of small open reading frame (sORF)-encoded peptides (SEPs) is rapidly expanding the known proteome at the lower end of the size distribution1,2. Here, we show that the mitochondria proteome is enriched for proteins smaller than 100 a.a. (defined as SEPs). Using a mitochondrial prediction and validation pipeline for small open-reading-frame (sORF)-encoded peptides (SEPs), we report the discovery of 16 endogenous mitochondrial SEPs (mito-SEPs) associated with oxidative phosphorylation (OXPHOS). Through functional prediction, proteomics, metabolomics and metabolic flux modeling, we demonstrate that BRAWNIN (BR), a 71 amino acid peptide encoded by the C12orf73 gene, is essential for respiratory chain complex III (CIII) assembly. In human cells, BR is induced by the energy-sensing AMPK pathway, and its depletion impairs mitochondrial ATP production. In vivo, BR is enriched in muscle tissues and its maternal zygotic deletion in zebrafish causes complete CIII loss, resulting in severe growth retardation, lactic acidosis and early death. Our findings demonstrate that BR is essential for oxidative phosphorylation across vertebrate species. We propose that mito-SEPs are an untapped resource for essential regulators of oxidative metabolism.

Recovery of free ADP, Pi, and free energy of ATP hydrolysis in human skeletal muscle

1998 ◽  
Vol 85 (6) ◽  
pp. 2140-2145 ◽  
Author(s):  
Henning Wackerhage ◽  
Uwe Hoffmann ◽  
Dieter Essfeld ◽  
Dieter Leyk ◽  
Klaus Mueller ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Nuclear Magnetic Resonance ◽  
Free Energy ◽  
Magnetic Resonance ◽  
Oxidative Phosphorylation ◽  
Human Skeletal Muscle ◽  
Atp Hydrolysis ◽  
Resonance Spectroscopy ◽  
Atp Production ◽  
Production And Consumption

We measured significant undershoots of the concentrations of free ADP ([ADP]) and Pi([Pi]) and the free energy of ATP hydrolysis (Δ G ATP) below initial resting levels during recovery from severe ischemic exercise with 31P-nuclear magnetic resonance spectroscopy in 11 healthy sports students. Undershoots of the rate of oxidative phosphorylation would be predicted if the rate of oxidative phosphorylation would depend solely on free [ADP], [Pi], or Δ G ATP. However, undershoots of the rate of oxidative phosphorylation have not been reported in the literature. Furthermore, undershoots of the rate of oxidative phosphorylation are unlikely because there is evidence that a balance between ATP production and consumption cannot be achieved if an undershoot of the rate of oxidative phosphorylation actually occurs. Therefore, oxidative phosphorylation seems to depend not only on free [ADP], [Pi], or Δ G ATP. An explanation is that acidosis-related or other factors control oxidative phosphorylation additionally, at least under some conditions.

Relation between phosphate metabolites and oxygen consumption of heart in vivo

1989 ◽  
Vol 256 (1) ◽  
pp. H265-H274 ◽  
Author(s):  
L. A. Katz ◽  
J. A. Swain ◽  
M. A. Portman ◽  
R. S. Balaban
Keyword(s):  
Oxygen Consumption ◽  
Atp Hydrolysis ◽  
Respiratory Control ◽  
Creatine Phosphate ◽  
Canine Heart ◽  
Hydrolysis Products ◽  
Threefold Increase ◽  
Cooperativity Effects

The relation between induced increases in cardiac work and phosphate metabolites was investigated in the canine heart in vivo to evaluate the role of ATP hydrolysis products, ADP and inorganic phosphate (Pi), in the control of myocardial oxygen consumption (MVO2). In these studies, myocardial blood flow and oxygen consumption were simultaneously measured with the 31P-nuclear magnetic resonance (NMR)-detected phosphate metabolites. Three protocols were used to increase myocardial work: pacing, epinephrine, and phenylephrine infusions. When these protocols were used, no or only slight changes in myocardial ATP, Pi, and creatine phosphate were observed with a greater than threefold increase in MVO2. The calculated intracellular free Mg concentration, ADP, and pH were also only slightly affected by these increases in work. These data indicate that a simple model involving the feedback of cytosolic ADP and Pi to the mitochondria regulating respiration is inadequate to explain respiratory control in vivo. These data suggest that some other parameters or cooperativity effects involving the phosphate metabolites must play a role in the feedback between respiration and work in the heart in vivo.

Overtraining of aerobic physical exercise reduce rats (Rattus norvegicus) memory

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Ni Made Ridla Parwata
Keyword(s):  
Body Weight ◽  
Physical Exercise ◽  
Rattus Norvegicus ◽  
Research Method ◽  
Male Rat ◽  
Control Group ◽  
Adult Male Rat ◽  
The Subject ◽  
Heavy Training

Overtraining syndrome is a decrease in physical capacity, emotions and immunity due to training that is too often without adequate periods of rest. Overtraining is often experienced by athletes who daily undergo heavy training with short break periods. This research aims to look at the effect of overtraining aerobic physical exercise on memory in mice. The research method was experimental in vivo with the subject of adult male rat (Rattus Norvegicus) Winstar strain aged 8-10 weeks, body weight 200-250 gr. Divided into three groups, namely the control group, aerobic group and overtraining group. The results of memory tests with water E Maze showed an increase in the duration of travel time and the number of animal errors made by the overtraining group (p = 0.003). This study concludes that overtraining aerobic physical exercise can reduce memory in rat hippocampus.

Regulation of RNA helicase activity: principles and examples

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Pascal Donsbach ◽  
Dagmar Klostermeier
Keyword(s):  
Atp Hydrolysis ◽  
Wide Spectrum ◽  
Mrna Translation ◽  
Rna Degradation ◽  
Rna Helicases ◽  
Interaction Partners ◽  
Rna Duplexes ◽  
Self Association

Abstract RNA helicases are a ubiquitous class of enzymes involved in virtually all processes of RNA metabolism, from transcription, mRNA splicing and export, mRNA translation and RNA transport to RNA degradation. Although ATP-dependent unwinding of RNA duplexes is their hallmark reaction, not all helicases catalyze unwinding in vitro, and some in vivo functions do not depend on duplex unwinding. RNA helicases are divided into different families that share a common helicase core with a set of helicase signature motives. The core provides the active site for ATP hydrolysis, a binding site for the non-sequence-specific interactions with RNA, and in many cases a basal unwinding activity. Its activity is often regulated by flanking domains, by interaction partners, or by self-association. In this review, we summarize the regulatory mechanisms that modulate the activities of the helicase core. Case studies on selected helicases with functions in translation, splicing, and RNA sensing illustrate the various modes and layers of regulation in time and space that harness the helicase core for a wide spectrum of cellular tasks.

scholarly journals DisA Limits RecG Activities at Stalled or Reversed Replication Forks

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1357
Author(s):  
Rubén Torres ◽  
Carolina Gándara ◽  
Begoña Carrasco ◽  
Ignacio Baquedano ◽  
Silvia Ayora ◽  
...  
Keyword(s):  
Atp Hydrolysis ◽  
Holliday Junctions ◽  
Genome Integrity ◽  
Stable Complex ◽  
Dna Unwinding ◽  
Replication Forks ◽  
Dna Structures ◽  
Checkpoint Protein

The DNA damage checkpoint protein DisA and the branch migration translocase RecG are implicated in the preservation of genome integrity in reviving haploid Bacillus subtilis spores. DisA synthesizes the essential cyclic 3′, 5′-diadenosine monophosphate (c‑di-AMP) second messenger and such synthesis is suppressed upon replication perturbation. In vitro, c-di-AMP synthesis is suppressed when DisA binds DNA structures that mimic stalled or reversed forks (gapped forks or Holliday junctions [HJ]). RecG, which does not form a stable complex with DisA, unwinds branched intermediates, and in the presence of a limiting ATP concentration and HJ DNA, it blocks DisA-mediated c-di-AMP synthesis. DisA pre-bound to a stalled or reversed fork limits RecG-mediated ATP hydrolysis and DNA unwinding, but not if RecG is pre-bound to stalled or reversed forks. We propose that RecG-mediated fork remodeling is a genuine in vivo activity, and that DisA, as a molecular switch, limits RecG-mediated fork reversal and fork restoration. DisA and RecG might provide more time to process perturbed forks, avoiding genome breakage.

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