Substrate-specific impairment of mitochondrial respiration in permeabilized fibers from patients with coronary heart disease versus valvular disease

Duicu, Oana; Jusca, Calin; Falnita, Lucian; Mirica, Silvia Nicoleta; Maximov, Daniela; Fira-Mlădinescu, Ovidiu; Muntean, Daniela-Lucia

doi:10.1007/s11010-013-1644-4

Cited by 15 publications

(17 citation statements)

References 27 publications

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“…We have recently performed a similar study aimed at assessing the respiratory function in permeabilized fibres of human right atrial appendages harvested from patients with coronary heart disease vs. patients with valvular disease and preserved ejection fraction that underwent non-emergency cardiac surgery. Similarly to the previously mentioned data, we also found in coronary patients (but not in valvular ones) a significant decline for the oxidative phosphorylation capacity and respiratory control ratio for mitochondria energized with complex I (but not with complex II) substrates [24]. These observations are in the line with previous reports suggesting that treatments aimed at supporting cardiac mitochondria function might be able to mitigate electrical dysfunction in the heart [25].…”

Section: Mechanisms Of Atrial Remodelingsupporting

confidence: 92%

Atrial Remodeling in Permanent Atrial Fibrillation: Mechanisms and Pharmacological Implications

Muntean¹,

Kohajda²,

Fazekas

et al. 2013

J Clin Exp Cardiolog

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Atrial fibrillation (AF), the most prevalent rhythm disorder in clinical practice, is currently significantly contributing to morbidity and mortality of the ageing population. In the past decades, a tremendous amount of research resulted in valuable insights into AF pathophysiology, with a primary focus on atrial remodeling. Defined as a persistent change in atrial function and structure, remodeling has the intrinsic properties to enhance the probability of focal (ectopic) and/or re-entrant pursuits, thus supporting AF persistence. The hallmark of structural remodeling is represented by atrial fibrosis, a multifactorial process involving an interaction between neurohormonal and cellular mediators. This paper provides a brief summary of the recent knowledge with respect to electrical and structural remodeling and novel insights into the pathogenesis of atrial fibrosis. Since current drug options for AF treatment are far from being optimal we also discuss the therapeutic principles and current alternatives for counteracting atrial fibrosis, and thus preventing arrhythmia recurrence.

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Section: Mechanisms Of Atrial Remodelingsupporting

confidence: 92%

Atrial Remodeling in Permanent Atrial Fibrillation: Mechanisms and Pharmacological Implications

Muntean¹,

Kohajda²,

Fazekas

et al. 2013

J Clin Exp Cardiolog

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“…However, on PYR as substrate, the stimulation effect of different ADP levels was negligible. The OUR and stimulating effects of ADP determined in OUR study were in a similar range with literature data of permeabilized CHO cells [32], other mammalian cells [33][34][35][36], or isolated mitochondria from different tissues [37,38]. However, an absolute comparison between different studies is difficult since the respiration rates are specific for substrates or substrate combinations, tissue, species, and cell line and also dependent on experimental conditions and history of cells, for example the training state and fitness level of cells [31,39,40].…”

Section: Quantitative Comparison Of Different Mitochondrial Substratesupporting

confidence: 84%

High‐throughput respiration screening of single mitochondrial substrates using permeabilized CHO cells highlights control of mitochondria metabolism

Wahrheit

Nonnenmacher

Sperber

et al. 2015

Engineering in Life Sciences

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Respiration analysis using isolated mitochondria and electrochemical oxygen sensing has contributed significantly to the knowledge about mitochondrial metabolism, which is involved in energy generation but also in ageing and numerous diseases. Here, we present a high‐throughput respiration screening for functional in situ mitochondrial studies in permeabilized Chinese hamster ovary cells. The determination of oxygen uptake rates allowed a quantitative comparison between different conditions and a distinction of substrates into three groups providing an insight into tricarboxylic acid (TCA) cycle regulation. The mitochondrial metabolization of citrate, isocitrate, glutamine, and glutamate was highly stimulated by ADP supply. In contrast, the metabolization of α‐ketoglutarate, succinate, fumarate, and malate was little controlled by the energy and redox state. Metabolization of pyruvate was very strictly regulated by several independent mechanisms: phosphorylation, feedback inhibition, but also by the availability of CoA. A moderate stimulation of pyruvate metabolization was accomplished by feeding both pyruvate and aspartate simultaneously. The presented high‐throughput respiration screening provides comprehensive information about the effect of single or mixed substrates on mitochondrial metabolic activities, including transport and TCA cycle regulation, and metabolic bottlenecks. This supports the design of efficient mammalian producer strains or feeding strategies, but also the investigation of pathological and toxicological effects related to mitochondrial metabolism.

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“…Normal function of mitochondria and their pathological changes, including production of reactive oxygen species (ROS), are heavily dependent on the redox state of the electron transport chain (ETC) cytochromes and cytochrome c in particular 4 5 . At present, most of the studies of isolated mitochondria and mitochondria in cells are performed by fluorescent microscopy, absorption spectroscopy and measurements of O 2 consumption 3 6 7 8 . The fluorescent microscopy with small fluorescent dyes (rhodamin and MitoTracker-family, etc.)…”

mentioning

confidence: 99%

Probing cytochrome c in living mitochondria with surface-enhanced Raman spectroscopy

Brazhe

Evlyukhin

Goodilin

et al. 2015

Sci Rep

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Selective study of the electron transport chain components in living mitochondria is essential for fundamental biophysical research and for the development of new medical diagnostic methods. However, many important details of inter-and intramembrane mitochondrial processes have remained in shadow due to the lack of non-invasive techniques. Here we suggest a novel label-free approach based on the surface-enhanced Raman spectroscopy (SERS) to monitor the redox state and conformation of cytochrome c in the electron transport chain in living mitochondria. We demonstrate that SERS spectra of living mitochondria placed on hierarchically structured silver-ring substrates provide exclusive information about cytochrome c behavior under modulation of inner mitochondrial membrane potential, proton gradient and the activity of ATP-synthetase. Mathematical simulation explains the observed enhancement of Raman scattering due to high concentration of electric nearfield and large contact area between mitochondria and nanostructured surfaces.Mitochondria are organelles of fundamental importance for cellular energy production, metabolic regulation, aging and cell survival under stress [1][2][3] . Normal function of mitochondria and their pathological changes, including production of reactive oxygen species (ROS), are heavily dependent on the redox state of the electron transport chain (ETC) cytochromes and cytochrome c in particular 4,5 . At present, most of the studies of isolated mitochondria and mitochondria in cells are performed by fluorescent microscopy, absorption spectroscopy and measurements of O 2 consumption 3,[6][7][8] . The fluorescent microscopy with small fluorescent dyes (rhodamin and MitoTracker-family, etc.) or fluorescent proteins (GFP, YFP, RFP) can provide general information about changes in the potential of the inner mitochondrial membrane (Δ Φ ), the mitochondrial volume, and the co-localization of certain mitochondrial components with a molecule of interest

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Substrate-specific impairment of mitochondrial respiration in permeabilized fibers from patients with coronary heart disease versus valvular disease

Cited by 15 publications

References 27 publications

Atrial Remodeling in Permanent Atrial Fibrillation: Mechanisms and Pharmacological Implications

Atrial Remodeling in Permanent Atrial Fibrillation: Mechanisms and Pharmacological Implications

High‐throughput respiration screening of single mitochondrial substrates using permeabilized CHO cells highlights control of mitochondria metabolism

Probing cytochrome c in living mitochondria with surface-enhanced Raman spectroscopy

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