scholarly journals Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Hélène Lemieux ◽  
Pierre U. Blier ◽  
Erich Gnaiger
Keyword(s):  
Electron Flow ◽  
Mouse Heart ◽  
Respiratory Capacity ◽  
Flow Through ◽  
Permeabilized Fibers ◽  
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 Inhibition of electron flow through complex I of the mitochondrial respiratory chain of Ehrlich ascites carcinoma cells by methylglyoxal

1994 ◽  
Vol 303 (1) ◽  
pp. 69-72 ◽  
Author(s):  
S Ray ◽  
S Dutta ◽  
J Halder ◽  
M Ray
Keyword(s):  
Oxygen Consumption ◽  
Respiratory Chain ◽  
Complex I ◽  
Electron Flow ◽  
Mitochondrial Respiratory Chain ◽  
Ehrlich Ascites Carcinoma ◽  
Inhibitory Effect ◽  
Ehrlich Ascites ◽  
Flow Through ◽  
Mitochondrial Respiratory

The effect of methylglyoxal on the oxygen consumption of Ehrlich-ascites-carcinoma (EAC)-cell mitochondria was tested by using different respiratory substrates, electron donors at different segments of the mitochondrial respiratory chain and site-specific inhibitors to identify the specific respiratory complex which might be involved in the inhibitory effect of methylglyoxal on the oxygen consumption by these cells. The results indicate that methylglyoxal strongly inhibits ADP-stimulated alpha-oxo-glutarate and malate plus pyruvate-dependent respiration, whereas, at a much higher concentration, methylglyoxal fails to inhibit succinate-dependent respiration. Methylglyoxal also fails to inhibit respiration which is initiated by duroquinol, an artificial electron donor. Moreover, methylglyoxal cannot inhibit oxygen consumption when the NNN'N′-tetramethyl-p-phenylenediamine by-pass is used. The inhibitory effect of methylglyoxal is identical on both ADP-stimulated and uncoupler-stimulated respiration. Lactaldehyde, a catabolite of methylglyoxal, can exert a protective effect on the inhibition of EAC-cell mitochondrial respiration by methylglyoxal. We suggest that methylglyoxal possibly inhibits the electron flow through complex I of the EAC-cell mitochondrial respiratory chain.

scholarly journals Atorvastatin impairs liver mitochondrial function in obese Göttingen Minipigs but heart and skeletal muscle are not affected

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Liselotte Bruun Christiansen ◽  
Tine Lovsø Dohlmann ◽  
Trine Pagh Ludvigsen ◽  
Ewa Parfieniuk ◽  
Michal Ciborowski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Function ◽  
Citrate Synthase ◽  
Obese Group ◽  
Control Group ◽  
Dependent Manner ◽  
Respiratory Capacity ◽  
Protein Carbonyl Content ◽  
Functional Changes ◽  
Mitochondrial Respiratory

AbstractStatins lower the risk of cardiovascular events but have been associated with mitochondrial functional changes in a tissue-dependent manner. We investigated tissue-specific modifications of mitochondrial function in liver, heart and skeletal muscle mediated by chronic statin therapy in a Göttingen Minipig model. We hypothesized that statins enhance the mitochondrial function in heart but impair skeletal muscle and liver mitochondria. Mitochondrial respiratory capacities, citrate synthase activity, coenzyme Q10 concentrations and protein carbonyl content (PCC) were analyzed in samples of liver, heart and skeletal muscle from three groups of Göttingen Minipigs: a lean control group (CON, n = 6), an obese group (HFD, n = 7) and an obese group treated with atorvastatin for 28 weeks (HFD + ATO, n = 7). Atorvastatin concentrations were analyzed in each of the three tissues and in plasma from the Göttingen Minipigs. In treated minipigs, atorvastatin was detected in the liver and in plasma. A significant reduction in complex I + II-supported mitochondrial respiratory capacity was seen in liver of HFD + ATO compared to HFD (P = 0.022). Opposite directed but insignificant modifications of mitochondrial respiratory capacity were seen in heart versus skeletal muscle in HFD + ATO compared to the HFD group. In heart muscle, the HFD + ATO had significantly higher PCC compared to the HFD group (P = 0.0323). In the HFD group relative to CON, liver mitochondrial respiration decreased whereas in skeletal muscle, respiration increased but these changes were insignificant when normalizing for mitochondrial content. Oral atorvastatin treatment in Göttingen Minipigs is associated with a reduced mitochondrial respiratory capacity in the liver that may be linked to increased content of atorvastatin in this organ.

Abstract 102: Time-of-intake Regulates Glucocorticoid Pharmacology Of Cardiac Bioenergetics

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Mattia Quattrocelli ◽  
Michelle Wintzinger ◽  
Karen Miz
Keyword(s):  
Ex Vivo ◽  
Gene Knockout ◽  
Heart Tissue ◽  
Functional Coupling ◽  
Specific Gene ◽  
Heart Metabolism ◽  
Respiratory Capacity ◽  
Circadian Time ◽  
The Impact ◽  
Mitochondrial Respiratory

Glucocorticoid steroids are circadian regulators of energy balance. However, the specific direct effects of glucocorticoids on heart metabolism remain unresolved. Moreover, the impact of circadian time-of-intake on glucocorticoid pharmacology is still unknown. Here, we investigated whether circadian time of exposure gates the effects of synthetic glucocorticoids on heart bioenergetics. We compared the effects of diurnal versus nocturnal glucocorticoids in heart tissue and mitochondria from wildtype mice, controlling the subjective circadian time of drug injection. To avoid interferences from other tissues, we developed an ex vivo system to interrogate the mitochondrial respiratory capacity rate (state III/state IV) in isolated hearts. We found that diurnal but not nocturnal pulse of the glucocorticoid prednisone increased the mitochondrial respiratory capacity rate in heart. This correlated with circadian-restricted effects on mitochondrial abundance. This was remarkable as it contrasts the circadian fluctuations of endogenous glucocorticoids. Using transgenic mice with inducible cardiac-specific gene knockout, we found that the bioenergetic effects of diurnal-restricted prednisone were dependent on the glucocorticoid receptor and its co-factor Kruppel-like factor 15. Considering the bioenergetic decline that hallmarks the aging heart, we asked whether these circadian-gated effects were applicable to aged mice. We therefore treated 24 months-old mice for 12 weeks with a diurnal-restricted regimen of prednisone. Compared to vehicle, diurnal prednisone increased mitochondrial respiration along with NAD + and ATP content in aged hearts. Moreover, lipidomic profiling of myocardial tissue showed that the vast majority of lipids were downregulated after treatment, including triacylglycerols, suggesting a functional coupling between lipid utilization and mitochondrial oxidation in treated hearts. We also found that diurnal-restricted prednisone rescued bioenergetics and improved function in diabetic hearts from db/db mice. In summary, our data indicate that glucocorticoids regulate cardiac bioenergetics according to circadian-time of intake, supporting a role for chrono-pharmacology in aged and diabetic hearts.

Leucine augments specific skeletal muscle mitochondrial respiratory pathways during recovery following 7 days of physical inactivity in older adults

2021 ◽  
Author(s):  
Emily J. Arentson-Lantz ◽  
Jasmine Mikovic ◽  
Nisha Bhattarai ◽  
Christopher S. Fry ◽  
Séverine Lamon ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Bed Rest ◽  
Metabolic Clearance ◽  
Leucine Supplementation ◽  
Respiratory Capacity ◽  
Antioxidant Defense Systems ◽  
Mitochondrial Respiratory

Leucine supplementation attenuates the loss of skeletal muscle mass and function in older adults during bed rest. We sought to determine if leucine could also preserve and/or restore mitochondrial function and muscle oxidative capacity during periods of disuse and rehabilitation. Healthy older adults (69.1 ± 1.1 years) consumed a structured diet with supplemental leucine (LEU: 0.06 g/ kg body weight/ meal; n=8) or alanine (CON: 0.06 g/ kg body weight/meal; n=8) during 7 days of bed rest and 5 days of inpatient rehabilitation. A 75 g oral glucose tolerance test was performed at baseline (PreBR), after bed rest (PostBR) and rehabilitation (PostRehab) and used to calculate an indicator of insulin sensitivity, metabolic clearance rate. (MCR). Tissue samples from the m. vastus lateralis were collected PreBR, PostBR, and PostRehab to assess mitochondrial respiratory capacity and protein markers of the oxidative phosphorylation and a marker of the antioxidant defense systems. During bed rest, leucine tended to preserve insulin sensitivity (Change in MCR, CON vs. LEU: -3.5 ± 0.82 vs LEU: -0.98 ± 0.88, p=0.054), but had no effect on mitochondrial respiratory capacity (Change in State 3+succinate CON vs. LEU -8.7 ± 6.1 vs. 7.3 ± 4.1 pmol O2/sec/mg tissue, p=0.10) Following rehabilitation, leucine increased ATP-linked respiration (CON vs. LEU: -8.9 ± 6.2 vs. 15.5± 4.4 pmol O2/sec/mg tissue, p=0.0042). While the expression of mitochondrial respiratory and antioxidant proteins was not impacted, leucine supplementation preserved specific pathways of mitochondrial respiration, insulin sensitivity and a marker of oxidative stress during bed rest and rehabilitation.

scholarly journals The C Termini of Constitutive Nitric-oxide Synthases Control Electron Flow through the Flavin and Heme Domains and Affect Modulation by Calmodulin

2000 ◽  
Vol 275 (38) ◽  
pp. 29225-29232 ◽  
Author(s):  
Linda J. Roman ◽  
Pavel Martásek ◽  
R. Timothy Miller ◽  
Dawn E. Harris ◽  
Melissa A. de la Garza ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Electron Flow ◽  
Nitric Oxide Synthases ◽  
Flow Through

Electron Flow through Geometrical Discontinuity in Coaxial Magnetically Insulated Transmission Lines

2000 ◽  
Vol 39 (Part 1, No. 9A) ◽  
pp. 5280-5286 ◽  
Author(s):  
Kazuki Hiraoka ◽  
Mitsuo Nakajima ◽  
Makoto Shiho ◽  
Kazuhiko Horioka
Keyword(s):  
Transmission Lines ◽  
Electron Flow ◽  
Flow Through ◽  
Geometrical Discontinuity
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