Mitochondrial respiratory control and early defects of oxidative phosphorylation in the failing human heart

2011 ◽  
Vol 43 (12) ◽  
pp. 1729-1738 ◽  
Author(s):  
Hélène Lemieux ◽  
Severin Semsroth ◽  
Herwig Antretter ◽  
Daniel Höfer ◽  
Erich Gnaiger
Keyword(s):  
Oxidative Phosphorylation ◽  
Human Heart ◽  
Respiratory Control ◽  
Mitochondrial Respiratory

scholarly journals Remodeling Pathway Control of Oxidative Phosphorylation by Temperature in the Heart

2017 ◽  
Author(s):  
Hélène Lemieux ◽  
Pierre U. Blier ◽  
Erich Gnaiger
Keyword(s):  
Oxidative Phosphorylation ◽  
Electron Flow ◽  
Respiratory Control ◽  
Muscle Performance ◽  
Mouse Heart ◽  
Strong Temperature Dependence ◽  
Excess Capacity ◽  
Respiratory Capacity ◽  
Disease Evolution ◽  
Mitochondrial Respiratory

AbstractThe capacity of mitochondrial oxidative phosphorylation (OXPHOS) and fuel substrate supply are key determinants of cardiac muscle performance. Although temperature exerts a strong effect on energy metabolism, until recently numerous respiratory studies of mammalian mitochondria have been carried out below physiological temperature, with substrates supporting submaximal respiratory capacity. We measured mitochondrial respiration as a function of temperature in permeabilized fibers from the left ventricle of the mouse heart. At 37 °C, OXPHOS capacity with electron entry through either Complex I or Complex II into the Q-junction was about half of respiratory capacity with the corresponding physiological substrate combination reconstituting tricarboxylic acid cycle function with convergent electron flow through the NADH&succinate (NS) pathway. When separating the component core mitochondrial pathways, the relative contribution of the NADH pathway increased with a decrease of temperature from 37 to 25 ºC. The additive effect of convergent electron flow has profound consequences for optimization of mitochondrial respiratory control. The apparent excess capacity of cytochrome c oxidase (CIV) was 0.7 above convergent NS-pathway capacity, but would be overestimated nearly 2-fold with respect to respiration restricted by provision of NADH-linked substrates only. The apparent excess capacity of CIV increased sharply at 4 °C, caused by a strong temperature dependence of and OXPHOS limitation by NADH-linked dehydrogenases. This mechanism of mitochondrial respiratory control in the hypothermic mammalian heart is comparable to the pattern in ectotherm species, pointing towards NADH-linked mt-matrix dehydrogenases and the phosphorylation system rather than electron transfer complexes as the primary drivers of thermal sensitivity at low temperature and likely modulators of temperature adaptation and acclimatization. Delineating the link between stress and remodeling of OXPHOS is critically important for improving our understanding of metabolic perturbations in disease evolution and cardiac protection. Temperature is not a trivial experimental parameter to consider when addressing these questions.

scholarly journals Senescence-associated changes in respiration and oxidative phosphorylation in primary human fibroblasts

2004 ◽  
Vol 380 (3) ◽  
pp. 919-928 ◽  
Author(s):  
Eveline HUTTER ◽  
Kathrin RENNER ◽  
Gerald PFISTER ◽  
Petra STÖCKL ◽  
Pidder JANSEN-DÜRR ◽  
...  
Keyword(s):  
Electron Transport ◽  
Oxidative Phosphorylation ◽  
Replicative Senescence ◽  
Citrate Synthase ◽  
Human Fibroblasts ◽  
Respiratory Control ◽  
Compensatory Mechanisms ◽  
Intact Cells ◽  
Atp Production ◽  
Human Diploid Fibroblasts

Limitation of lifespan in replicative senescence is related to oxidative stress, which is probably both the cause and consequence of impaired mitochondrial respiratory function. The respiration of senescent human diploid fibroblasts was analysed by highresolution respirometry. To rule out cell-cycle effects, proliferating and growth-arrested young fibroblasts were used as controls. Uncoupled respiration, as normalized to citrate synthase activity, remained unchanged, reflecting a constant capacity of the respiratory chain. Oligomycin-inhibited respiration, however, was significantly increased in mitochondria of senescent cells, indicating a lower coupling of electron transport with phosphorylation. In contrast, growth-arrested young fibroblasts exhibited a higher coupling state compared with proliferating controls. In intact cells, partial uncoupling may lead to either decreased oxidative ATP production or a compensatory increase in routine respiration. To distinguish between these alternatives, we subtracted oligomycin-inhibited respiration from routine respiration, which allowed us to determine the part of respiratory activity coupled with ATP production. Despite substantial differences in the respiratory control ratio, ranging from 4 to 11 in the different experimental groups, a fixed proportion of respiratory capacity was maintained for coupled oxidative phosphorylation in all the experimental groups. This finding indicates that the senescent cells fully compensate for increased proton leakage by enhanced electron-transport activity in the routine state. These results provide a new insight into age-associated defects in mitochondrial function and compensatory mechanisms in intact cells.

Oxidative phosphorylation in cardiac infarct. Effect of glucose-KCl-insulin solution

1965 ◽  
Vol 209 (2) ◽  
pp. 371-375 ◽  
Author(s):  
Edmundo Calva ◽  
Adela Mujica ◽  
Abdo Bisteni ◽  
Demetrio Sodi-Pallares
Keyword(s):  
Oxygen Consumption ◽  
Oxidative Phosphorylation ◽  
Respiratory Control ◽  
Low Oxygen ◽  
Normal Limits ◽  
Functional Aspects ◽  
Insulin Solution ◽  
Effect Of Glucose ◽  
Infarcted Tissue ◽  
Electrocardiographic Abnormalities

Myocardial infarction was produced in dogs by ligature of the anterior descending coronary artery. Sarcosomes were isolated from normal and infarcted tissue. Oxygen consumption was followed polarographically and adenosine triphosphate was measured as glucose 6-phosphate. One group of animals received a continuous infusion of glucose for 12 hr; another group received "polarizing solution" (glucose-KCl-insulin). Sarcosomes from the first had a low oxygen consumption, no respiratory control, and no oxidative phosphorylation. In contrast, the administration of glucose-KCl-insulin solution maintained practically within normal limits these functional aspects of the sarcosomes. The reversal of electrocardiographic abnormalities by the administration of the polarizing solution coincided with improvement of such biochemical functions. Anesthesia and surgical handling did not appear to modify the behavior of the sarcosomes.

Mitochondrial respiratory control can compensate for intracellular O2 gradients in cardiomyocytes at low Po 2

2002 ◽  
Vol 283 (3) ◽  
pp. H871-H878 ◽  
Author(s):  
Eiji Takahashi ◽  
Koji Asano
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Diffusion ◽  
Respiratory Control ◽  
Oxygen Gradients ◽  
Nadh Fluorescence ◽  
Carbonyl Cyanide ◽  
Intrinsic Regulation ◽  
Electrical Pacing ◽  
Mitochondrial Oxidative Metabolism ◽  
Mitochondrial Respiratory

In isolated single cardiomyocytes with moderately elevated mitochondrial respiration, direct evidence for intracellular radial gradients of oxygen concentration was obtained by subcellular spectrophotometry of myoglobin (Mb). When oxygen consumption was increased by carbonyl cyanide m-chlorophenylhydrazone (CCCP) during superfusion of cells with 4% oxygen, Po 2 at the cell core dropped to 2.3 mmHg, whereas Mb near the plasma membrane was almost fully saturated with oxygen. Subcellular NADH fluorometry demonstrated corresponding intracellular heterogeneities of NADH, indicating suppression of mitochondrial oxidative metabolism due to relatively slow intracellular oxygen diffusion. When oxygen consumption was increased by electrical pacing in 2% oxygen, radial oxygen gradients of similar magnitude were demonstrated (cell core Po 2 = 2.6 mmHg). However, an increase in NADH fluorescence at the cell core was not detected. Because CCCP abolished mitochondrial respiratory control while it was intact in electrically paced cardiomyocytes, we conclude that mitochondria with intact respiratory control can sustain electron transfer with reduced oxygen supply. Thus mitochondrial intrinsic regulation can compensate for relatively slow oxygen diffusion within cardiomyocytes.

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