scholarly journals Substrate- and Calcium-Dependent Differential Regulation of Mitochondrial Oxidative Phosphorylation and Energy Production in the Heart and Kidney

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 131
Author(s):  
Xiao Zhang ◽  
Namrata Tomar ◽  
Sunil M. Kandel ◽  
Said H. Audi ◽  
Allen W. Cowley ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Mitochondrial Respiration ◽  
Atp Synthesis ◽  
Heart Mitochondria ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Inhibitory Effects ◽  
Atp Production ◽  
Calcium Dependent ◽  
Palmitoyl Carnitine ◽  
Regulatory Effects

Mitochondrial dehydrogenases are differentially stimulated by Ca2+. Ca2+ has also diverse regulatory effects on mitochondrial transporters and other enzymes. However, the consequences of these regulatory effects on mitochondrial oxidative phosphorylation (OxPhos) and ATP production, and the dependencies of these consequences on respiratory substrates, have not been investigated between the kidney and heart despite the fact that kidney energy requirements are second only to those of the heart. Our objective was, therefore, to elucidate these relationships in isolated mitochondria from the kidney outer medulla (OM) and heart. ADP-induced mitochondrial respiration was measured at different CaCl2 concentrations in the presence of various respiratory substrates, including pyruvate + malate (PM), glutamate + malate (GM), alpha-ketoglutarate + malate (AM), palmitoyl-carnitine + malate (PCM), and succinate + rotenone (SUC + ROT). The results showed that, in both heart and OM mitochondria, and for most complex I substrates, Ca2+ effects are biphasic: small increases in Ca2+ concentration stimulated, while large increases inhibited mitochondrial respiration. Furthermore, significant differences in substrate- and Ca2+-dependent O2 utilization towards ATP production between heart and OM mitochondria were observed. With PM and PCM substrates, Ca2+ showed more prominent stimulatory effects in OM than in heart mitochondria, while with GM and AM substrates, Ca2+ had similar biphasic regulatory effects in both OM and heart mitochondria. In contrast, with complex II substrate SUC + ROT, only inhibitory effects on mitochondrial respiration was observed in both the heart and the OM. We conclude that the regulatory effects of Ca2+ on mitochondrial OxPhos and ATP synthesis are biphasic, substrate-dependent, and tissue-specific.

AN ENZYMATIC EVALUATION OF THIOL RADIOPROTECTORS

1966 ◽  
Vol 44 (3) ◽  
pp. 319-330 ◽  
Author(s):  
J. F. Scaife
Keyword(s):  
Oxidative Phosphorylation ◽  
Mitochondrial Respiration ◽  
Test System ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Atp Level ◽  
Normal Tissues ◽  
Mixed Disulfide ◽  
Liver Homogenates ◽  
Protection Theory

A number of thiol and disulfide compounds have been tested for their ability to inhibit the oxidation of α-ketoglutarate by rat-liver homogenates. In general, a correlation exists between the degree of inhibition and the radioprotective ability of the compound. It is possible that a better correlation exists for the corresponding disulfides.The inhibition involves oxidation of the thiol, and the disulfides were found to be more potent inhibitors than the thiols.There is no change in the ATP level of normal tissues after the administration of aminoethylisothiouronium bromide hydrobromide in vivo, and the protective ability of this compound is not considered to be related to any interference with mitochondrial oxidative phosphorylation. Mitochondrial respiration is, however, inhibited. The results support the mixed disulfide protection theory of Eldjarn and Pihl, and provide a physiologically significant test system for this hypothesis.

scholarly journals Higd1a is a positive regulator of cytochrome c oxidase

2015 ◽  
Vol 112 (5) ◽  
pp. 1553-1558 ◽  
Author(s):  
Takaharu Hayashi ◽  
Yoshihiro Asano ◽  
Yasunori Shintani ◽  
Hiroshi Aoyama ◽  
Hidetaka Kioka ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Structural Changes ◽  
Regulatory Mechanism ◽  
Atp Synthesis ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Domain Family ◽  
Raman Analysis ◽  
Atp Production ◽  
Positive Regulator ◽  
Inducible Genes

Cytochrome c oxidase (CcO) is the only enzyme that uses oxygen to produce a proton gradient for ATP production during mitochondrial oxidative phosphorylation. Although CcO activity increases in response to hypoxia, the underlying regulatory mechanism remains elusive. By screening for hypoxia-inducible genes in cardiomyocytes, we identified hypoxia inducible domain family, member 1A (Higd1a) as a positive regulator of CcO. Recombinant Higd1a directly integrated into highly purified CcO and increased its activity. Resonance Raman analysis revealed that Higd1a caused structural changes around heme a, the active center that drives the proton pump. Using a mitochondria-targeted ATP biosensor, we showed that knockdown of endogenous Higd1a reduced oxygen consumption and subsequent mitochondrial ATP synthesis, leading to increased cell death in response to hypoxia; all of these phenotypes were rescued by exogenous Higd1a. These results suggest that Higd1a is a previously unidentified regulatory component of CcO, and represents a therapeutic target for diseases associated with reduced CcO activity.

scholarly journals Relationships between the neuronal sodium/potassium pump and energy metabolism. Effects of K+, Na+, and adenosine triphosphate in isolated brain synaptosomes.

1990 ◽  
Vol 95 (4) ◽  
pp. 591-616 ◽  
Author(s):  
M Erecińska ◽  
F Dagani
Keyword(s):  
Oxidative Phosphorylation ◽  
Adenosine Triphosphate ◽  
Lactate Production ◽  
Atp Synthesis ◽  
Adenosine Monophosphate ◽  
Direct Stimulation ◽  
Secondary Importance ◽  
Atp Production ◽  
Moving Force ◽  
Brain Synaptosomes

The relationships between Na/K pump activity and adenosine triphosphate (ATP) production were determined in isolated rat brain synaptosomes. The activity of the enzyme was modulated by altering [K+]e, [Na+]i, and [ATP]i while synaptosomal oxygen uptake and lactate production were measured simultaneously. KCl increased respiration and glycolysis with an apparent Km of about 1 mM which suggests that, at the [K+]e normally present in brain, 3.3-4 mM, the pump is near saturation with this cation. Depolarization with 6-40 mM KCl had negligible effect on ouabain-sensitive O2 uptake indicating that at the voltages involved the activity of the Na/K ATPase is largely independent of membrane potential. Increases in [Na+]i by addition of veratridine markedly enhanced glycoside-inhibitable respiration and lactate production. Calculations of the rates of ATP synthesis necessary to support the operation of the pump showed that greater than 90% of the energy was derived from oxidative phosphorylation. Consistent with this: (a) the ouabain-sensitive Rb/O2 ratio was close to 12 (i.e., Rb/ATP ratio of 2); (b) inhibition of mitochondrial ATP synthesis by Amytal resulted in a decrease in the glycoside-dependent rate of 86Rb uptake. Analyses of the mechanisms responsible for activation of the energy-producing pathways during enhanced Na and K movements indicate that glycolysis is predominantly stimulated by increase in activity of phosphofructokinase mediated via a rise in the concentrations of adenosine monophosphate [AMP] and inorganic phosphate [Pi] and a fall in the concentration of phosphocreatine [PCr]; the main moving force for the elevation in mitochondrial ATP generation is the decline in [ATP]/[ADP] [Pi] (or equivalent) and consequent readjustments in the ratio of the intramitochondrial pyridine nucleotides [( NAD]m/[NADH]m). Direct stimulation of pyruvate dehydrogenase by calcium appears to be of secondary importance. It is concluded that synaptosomal Na/K pump is fueled primarily by oxidative phosphorylation and that a fall in [ATP]/[ADP][Pi] is the chief factor responsible for increased energy production.

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 Role of Plant Cell Conditioned Medium in the Phenotypic Expression of Nitrogenase Activity of Rhizobium trifolii Strain T1

1980 ◽  
Vol 33 (5) ◽  
pp. 613 ◽  
Author(s):  
Minocher Reporter ◽  
Mary L Skotnicki ◽  
Barry G Rolfe
Keyword(s):  
Oxidative Phosphorylation ◽  
Conditioned Medium ◽  
Plant Cell ◽  
Nitrogenase Activity ◽  
Phenotypic Expression ◽  
Atp Synthesis ◽  
Atp Production ◽  
Cell Conditioned Medium

The influence of substances from a conditioned medium of cultured plant cells on nitrogenase activity, respiration and ATP synthesis was investigated in R. tri/olii strain Tl. Nitrogenase activity in strain Tl was dependent on the addition of the plant cell conditioned medium. Studies showed that the initial effects of the plant substances on rhizobial cells was to increase their respiration rate and ATP production. Mutants of strain Tl which were uncoupled in their oxidative phosphorylation, were also tested. However, the plant factors had no effect on respiration and ATP synthesis and also failed to elicit in vitro nitrogenase activity in these mutants. It is proposed that these plant factors act by increasing the efficiency of oxidative phosphorylation, making more ATP available, and thus stimulating nitrogenase activity of R. tri/olii cells.

scholarly journals A drastic shift in the energetic landscape of toothed whale sperm cells

2021 ◽  
Author(s):  
L. Q. Alves ◽  
R. Ruivo ◽  
R. Valente ◽  
M. M. Fonseca ◽  
A. M. Machado ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Oxidative Phosphorylation ◽  
Sperm Motility ◽  
Sperm Cells ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Endogenous Fatty Acid ◽  
Atp Production ◽  
Spermatozoa Motility ◽  
Toothed Whale

AbstractMammalia spermatozoa are a notable example of energetic compartmentalization. While mitochondrial oxidative phosphorylation is restricted to the midpiece, sperm-specific glycolysis operates in the flagellum. Consequently, these highly specialized cells exhibit a clear adaptability to fuel substrates. This plasticity is essential to ensure sperm motility, and is known to vary among species. Here we describe an extreme example of spermatozoa-energetics adaptation. We show that toothed whales exhibit impaired sperm glycolysis, due to gene and exon erosion, and demonstrate that dolphin spermatozoa motility depends uniquely on endogenous fatty acid β-oxidation, but not carbohydrates. Our findings substantiate the observation of large mitochondria in spermatozoa, possibly boosting ATP production from endogenous fatty acids. This unique energetic rewiring emphasizes the physiological body reorganisation imposed by the carbohydrate-depleted marine environment.

scholarly journals Lichen fungi do not depend on the alga for ATP production

2021 ◽  
Author(s):  
Gulnara Tagirdzhanova ◽  
John McCutcheon ◽  
Toby Spribille
Keyword(s):  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Mitochondrial Genomes ◽  
Symbiotic Association ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Gene Encoding ◽  
Apparent Lack ◽  
Atp Production

Lichen fungi live in a symbiotic association with unicellular phototrophs and have no known aposymbiotic stage. A recent study postulated that some of them have lost mitochondrial oxidative phosphorylation and rely on their algal partners for ATP. This claim originated from an apparent lack of ATP9, a gene encoding one subunit of ATP synthase, from a few mitochondrial genomes. Here we show that while these fungi indeed have lost the mitochondrial ATP9, each retain a nuclear copy of this gene. Our analysis reaffirms that lichen fungi produce their own ATP.

scholarly journals Stimulation of Alpha1-Adrenergic Receptor Ameliorates Cellular Functions of Multiorgans beyond Vasomotion through PPARδ

PPAR Research ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-21
Author(s):  
Yong-Jik Lee ◽  
Hyun Soo Kim ◽  
Hong Seog Seo ◽  
Jin Oh Na ◽  
You-Na Jang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Oxidative Phosphorylation ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Biological Effects ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Spontaneously Hypertensive ◽  
Atp Production ◽  
Multiple Organs ◽  
Organ Specific

Cells can shift their metabolism between glycolysis and oxidative phosphorylation to enact their cell fate program in response to external signals. Widely distributed α1-adrenergic receptors (ARs) are physiologically stimulated during exercise, were reported to associate with the activating energetic AMPK pathway, and are expected to have biological effects beyond their hemodynamic effects. To investigate the effects and mechanism of AR stimulation on the physiology of the whole body, various in vitro and in vivo experiments were conducted using the AR agonist midodrine, 2-amino-N-[2-(2,5-dimethoxyphenyl)-2-hydroxy-ethyl]-acetamide. The expression of various biomarkers involved in ATP production was estimated through Western blotting, reverse transcription polymerase chain reaction, oxygen consumption rate, enzyme-linked immunosorbent assay (ELISA), fluorescence staining, and Oil red O staining in several cell lines (skeletal muscle, cardiac muscle, liver, macrophage, vascular endothelial, and adipose cells). In spontaneously hypertensive rats, blood pressure, blood analysis, organ-specific biomarkers, and general biomolecules related to ATP production were measured with Western blot analysis, immunohistochemistry, ELISA, and echocardiography. Pharmacological activation of α1-adrenergic receptors in C2C12 skeletal muscle cells promoted mitochondrial oxidative phosphorylation and ATP production by increasing the expression of catabolic molecules, including PPARδ, AMPK, and PGC-1α, through cytosolic calcium signaling and increased GLUT4 expression, as seen in exercise. It also activated those energetic molecules and mitochondrial oxidative phosphorylation with cardiomyocytes, endothelial cells, adipocytes, macrophages, and hepatic cells and affected their relevant cell-specific biological functions. All of those effects occurred around 3 h (and peaked 6 h) after midodrine treatment. In spontaneously hypertensive rats, α1-adrenergic receptor stimulation affected mitochondrial oxidative phosphorylation and ATP production by activating PPARδ, AMPK, and PGC-1α and the relevant biologic functions of multiple organs, suggesting organ crosstalk. The treatment lowered blood pressure, fat and body weight, cholesterol levels, and inflammatory activity; increased ATP content and insulin sensitivity in skeletal muscles; and increased cardiac contractile function without exercise training. These results suggest that the activation of α1-adrenergic receptor stimulates energetic reprogramming via PPARδ that increases mitochondrial oxidative phosphorylation and has healthy and organ-specific biological effects in multiple organs, including skeletal muscle, beyond its vasomotion effect. In addition, the action mechanism of α1-adrenergic receptor may be mainly exerted via PPARδ.

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