scholarly journals Mitochondrial Bioenergetics in Different Pathophysiological Conditions

2021 ◽  
Vol 22 (14) ◽  
pp. 7562
Author(s):  
Daniela Valenti ◽  
Anna Atlante
Keyword(s):  
Oxidative Phosphorylation ◽  
Mitochondrial Bioenergetics ◽  
Primary Role ◽  
Bioenergy Production ◽  
Cellular Life ◽  
Intracellular Organelles

Mitochondria are complex intracellular organelles involved in many aspects of cellular life, with a primary role in bioenergy production via oxidative phosphorylation (OXPHOS) [...]

scholarly journals Mitochondrial Structure and Bioenergetics in Normal and Disease Conditions

2021 ◽  
Vol 22 (2) ◽  
pp. 586
Author(s):  
Margherita Protasoni ◽  
Massimo Zeviani
Keyword(s):  
Energy Demand ◽  
Drug Targets ◽  
Mitochondrial Diseases ◽  
High Energy ◽  
Primary Role ◽  
Cellular Life ◽  
Mitochondrial Defects ◽  
Intracellular Organelles ◽  
Definition Of ◽  
Almost All

Mitochondria are ubiquitous intracellular organelles found in almost all eukaryotes and involved in various aspects of cellular life, with a primary role in energy production. The interest in this organelle has grown stronger with the discovery of their link to various pathologies, including cancer, aging and neurodegenerative diseases. Indeed, dysfunctional mitochondria cannot provide the required energy to tissues with a high-energy demand, such as heart, brain and muscles, leading to a large spectrum of clinical phenotypes. Mitochondrial defects are at the origin of a group of clinically heterogeneous pathologies, called mitochondrial diseases, with an incidence of 1 in 5000 live births. Primary mitochondrial diseases are associated with genetic mutations both in nuclear and mitochondrial DNA (mtDNA), affecting genes involved in every aspect of the organelle function. As a consequence, it is difficult to find a common cause for mitochondrial diseases and, subsequently, to offer a precise clinical definition of the pathology. Moreover, the complexity of this condition makes it challenging to identify possible therapies or drug targets.

Abstract 331: Recovery of Mitochondrial Bioenergetics after Hypoxia via Regulating Pyruvate Dehydrogenase Kinase and Adenosine Monophosphate-activated Kinase

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Jessica M Toli ◽  
Minzhen He ◽  
Carolyn Suzuki ◽  
Maha Abdellatif
Keyword(s):  
Fatty Acid ◽  
Oxidative Phosphorylation ◽  
Cardiac Myocytes ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Kinase ◽  
Neonatal Rat ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Mitochondrial Bioenergetics ◽  
Peroxisome Proliferator Activated Receptor

Mitochondrial quality control is critical for the survival of cardiac myocytes during stress. The purpose of this study was to examine the effect of metabolic substrates and regulators of metabolism on mitochondrial bioenergetics, as an indicator of mitochondrial quality, and how these factors might influence the recovery of the cell’s bioenergetics after hypoxia/ischemia. By monitoring oxygen consumption rates (OCR), in real-time, in live neonatal rat myocytes and human cardiac myocyte-differentiated induced pluripotent stem cells, we found that both cell types can maintain basal OCR efficiently with any metabolic substrate; however, the neonatal cells require both glucose and fatty acid, while the human adult cells require fatty acid only, for mounting maximum reserve respiratory capacity (RRC). Our data also show that subjecting cardiac myocytes to hypoxia results in a reduction of the cells’ basal OCR and oxidative phosphorylation, and exhausts the RRC, which is accompanied by an increase in pyruvate dehydrogenase kinase (Pdk) 1 and 4. Except for normalization of Pdk1 levels, there was little or no recovery of these parameters after reoxygenation. We, thus, hypothesized, that inhibition of Pdks may help recovery of the cell’s bioenergetics. Indeed, our results show that by inhibiting Pdks with dichloroacetate (DCA) before or after hypoxia, the cells’ bioenergetics, including OCR, oxidative phosphorylation, and RRC in neonatal myocytes, and RRC in the human myocytes fully recover within 24 h. On the other hand, activating AMP-activated kinase (AMPK) resulted in delayed (96 h) improvement of the cells’ RRC that was accompanied by an increase in peroxisome proliferator-activated receptor gamma, coactivator 1α (3.5x), peroxisome proliferator-activated receptor-α (2x), and mitochondrial number (2x). These results led us to conclude that compromised mitochondrial quality can be rescued through mechanisms that regulate glucose or fatty acid oxidation by either inhibiting Pdks or activating AMPK, respectively, in rodent and human myocytes.

scholarly journals Eugenia uniflora leaf essential oil promotes mitochondrial dysfunction in Drosophila melanogaster through the inhibition of oxidative phosphorylation

2017 ◽  
Vol 6 (4) ◽  
pp. 526-534 ◽  
Author(s):  
Nélson R. de Carvalho ◽  
Nathane R. Rodrigues ◽  
Giulianna E. Macedo ◽  
Ivi J. Bristot ◽  
Aline A. Boligon ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Essential Oil ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Bioenergetics ◽  
Eugenia Uniflora ◽  
Leaf Essential Oil

We evaluate the effects of Eugenia uniflora essential oil on mitochondrial bioenergetics in Drosophila melanogaster.

scholarly journals Improved method for isolation of coupled mitochondria of Araucaria angustifolia (Bert.) O. Kuntze

2004 ◽  
Vol 47 (6) ◽  
pp. 873-879 ◽  
Author(s):  
André Bellin Mariano ◽  
Leonardo Kovalhuk ◽  
Caroline Valente ◽  
Juliana Maurer-Menestrina ◽  
Adaucto Bellarmino Pereira-Netto ◽  
...  
Keyword(s):  
Oxygen Uptake ◽  
Oxidative Phosphorylation ◽  
Embryogenic Callus ◽  
Respiratory Control ◽  
Mitochondrial Bioenergetics ◽  
Respiratory Control Ratio ◽  
Araucaria Angustifolia ◽  
Improved Method ◽  
First Time

A method for the isolation of coupled mitochondria from the callus of Araucaria angustifolia is described for the first time. Mitochondria were isolated from embryogenic callus of A. angustifolia. They were metabolically active, able to sustain oxidative phosphorylation as shown by respiratory control ratio values, which were about 2.4 when respiring on succinate as substrate. Oxygen uptake experiments, using freeze-thawed disrupted mitochondria, showed the presence of alternative rotenone-insensitive NAD(P)H dehydrogenases, which were stimulated by Ca2+. The procedure now described for the isolation of A. angustifolia mitochondria is an important new tool, allowing the investigation of mitochondrial bioenergetics and metabolism and physiology of plants.

Absence of Stereospecific Effects of Bupivacaine Isomers on Heart Mitochondrial Bioenergetics

2000 ◽  
Vol 93 (2) ◽  
pp. 456-462 ◽  
Author(s):  
François Sztark ◽  
Karine Nouette-Gaulain ◽  
Monique Malgat ◽  
Philippe Dabadie ◽  
Jean-Pierre Mazat
Keyword(s):  
Oxidative Phosphorylation ◽  
Adenosine Triphosphate ◽  
Respiratory Chain ◽  
Local Anesthetics ◽  
Complex I ◽  
Metabolic Effects ◽  
Lipid Solubility ◽  
Mitochondrial Bioenergetics ◽  
Myocardial Depression ◽  
Mitochondrial Energy Metabolism

Background Highly lipophilic local anesthetics interfere with mitochondrial energy metabolism. These metabolic effects could, in part, explain some toxic effects of local anesthetics, such as bupivacaine-induced myocardial depression. The purpose of this study was to compare the optically pure isomers of bupivacaine on heart mitochondrial bioenergetics. Methods Both bupivacaine enantiomers were tested on rat heart isolated mitochondria. Oxygen consumption, adenosine triphosphate synthesis, and enzymatic activities of the four complexes of the respiratory chain were measured. Results No significant differences were found between R(+)- and S(-)-bupivacaine on mitochondrial oxidative phosphorylation with a similar dose-dependent decrease in adenosine triphosphate synthesis. Complex I (nicotinamide adenine dinucleotide ubiquinone reductase) was the enzymatic complex of the respiratory chain most sensitive to the bupivacaine isomers. Half-inhibitory concentrations for R(+)- and S(-)-bupivacaine were not statistically different (3.3 +/- 0.4 mm and 2.8 +/- 0.6 mm, respectively). Conclusions No stereospecific effects of bupivacaine enantiomers were shown in the inhibition of complex I activity and uncoupling of oxidative phosphorylation. This can be correlated with the lack of stereospecific effects of bupivacaine on myocardial depression. The lipid solubility of local anesthetics appears to be the principal physicochemical factor affecting the potency of these tertiary amines on mitochondrial bioenergetics.

scholarly journals Bioenergetic Changes during Differentiation of Human Embryonic Stem Cells along the Hepatic Lineage

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Branden M. Hopkinson ◽  
Claus Desler ◽  
Mark Kalisz ◽  
Peter Siig Vestentoft ◽  
Lene Juel Rasmussen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Oxidative Phosphorylation ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Premature Aging ◽  
Mitochondrial Bioenergetics ◽  
Human Stem Cells ◽  
Full Understanding ◽  
Embryonic Origin

Mitochondrial dysfunction has been demonstrated to result in premature aging due to its effects on stem cells. Nevertheless, a full understanding of the role of mitochondrial bioenergetics through differentiation is still lacking. Here we show the bioenergetics profile of human stem cells of embryonic origin differentiating along the hepatic lineage. Our study reveals especially the transition between hepatic specification and hepatic maturation as dependent on mitochondrial respiration and demonstrates that even though differentiating cells are primarily dependent on glycolysis until induction of hepatocyte maturation, oxidative phosphorylation is essential at all stages of differentiation.

The ER chaperone calnexin controls mitochondrial positioning and respiration

2020 ◽  
Vol 13 (638) ◽  
pp. eaax6660 ◽  
Author(s):  
Tomás Gutiérrez ◽  
Hong Qi ◽  
Megan C. Yap ◽  
Nasser Tahbaz ◽  
Leanne A. Milburn ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Energy Balance ◽  
Oxidative Phosphorylation ◽  
Atpase Activity ◽  
Redox State ◽  
Glycolytic Pathway ◽  
Mitochondrial Bioenergetics ◽  
Cellular Energy ◽  
Er Chaperone ◽  
Oxidative Phosphorylation Pathway

Chaperones in the endoplasmic reticulum (ER) control the flux of Ca2+ ions into mitochondria, thereby increasing or decreasing the energetic output of the oxidative phosphorylation pathway. An example is the abundant ER lectin calnexin, which interacts with sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). We found that calnexin stimulated the ATPase activity of SERCA by maintaining its redox state. This function enabled calnexin to control how much ER Ca2+ was available for mitochondria, a key determinant for mitochondrial bioenergetics. Calnexin-deficient cells compensated for the loss of this function by partially shifting energy generation to the glycolytic pathway. These cells also showed closer apposition between the ER and mitochondria. Calnexin therefore controls the cellular energy balance between oxidative phosphorylation and glycolysis.

scholarly journals Kinetics and control of oxidative phosphorylation in rat liver mitochondria after dexamethasone treatment

2004 ◽  
Vol 382 (2) ◽  
pp. 491-499 ◽  
Author(s):  
Damien ROUSSEL ◽  
Jean-François DUMAS ◽  
Gilles SIMARD ◽  
Yves MALTHIÈRY ◽  
Patrick RITZ
Keyword(s):  
Membrane Potential ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Liver Mitochondria ◽  
Energetic Cost ◽  
Proton Leak ◽  
Mitochondrial Bioenergetics ◽  
Dexamethasone Treatment ◽  
And Control

The present investigation was undertaken in order to evaluate the contributions of ATP synthesis and proton leak reactions to the rate of active respiration of liver mitochondria, which is altered following dexamethasone treatment (1.5 mg/kg per day for 5 days). We applied top-down metabolic control analysis and its extension, elasticity analysis, to gain insight into the mechanisms of glucocorticoid regulation of mitochondrial bioenergetics. Liver mitochondria were isolated from dexamethasone-treated, pair-fed and control rats when in a fed or overnight fasted state. Injection of dexamethasone for 5 days resulted in an increase in the fraction of the proton cycle of phosphorylating liver mitochondria, which was associated with a decrease in the efficiency of the mitochondrial oxidative phosphorylation process in liver. This increase in proton leak activity occurred with little change in the mitochondrial membrane potential, despite a significant decrease in the rate of oxidative phosphorylation. Regulation analysis indicates that mitochondrial membrane potential homoeostasis is achieved by equal inhibition of the mitochondrial substrate oxidation and phosphorylation reactions in rats given dexamethasone. Our results also suggest that active liver mitochondria from dexamethasone-treated rats are capable of maintaining phosphorylation flux for cellular purposes, despite an increase in the energetic cost of mitochondrial ATP production due to increased basal proton permeability of the inner membrane. They also provide a complete description of the effects of dexamethasone treatment on liver mitochondrial bioenergetics.

scholarly journals Listeria monocytogenes requires cellular respiration for NAD+ regeneration and pathogenesis

2021 ◽  
Author(s):  
Rafael Rivera-Lugo ◽  
David Deng ◽  
Andrea Anaya-Sanchez ◽  
Sara Tejedor-Sanz ◽  
Valeria M Reyes Ruiz ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Oxidative Phosphorylation ◽  
Nadh Oxidase ◽  
Cellular Respiration ◽  
Bacterial Respiration ◽  
Infection Model ◽  
Primary Role ◽  
Growth Defects ◽  
Mouse Infection Model

Cellular respiration is essential for multiple bacterial pathogens and a validated antibiotic target. In addition to driving oxidative phosphorylation, bacterial respiration has a variety of ancillary functions that obscure its contribution to pathogenesis. We find here that the intracellular pathogen Listeria monocytogenes encodes two respiratory pathways which are partially functionally redundant and indispensable for pathogenesis. Loss of respiration decreased NAD+ regeneration, but this could be specifically reversed by heterologous expression of a water-forming NADH oxidase (NOX). NOX expression fully rescued intracellular growth defects and increased L. monocytogenes loads >1,000-fold in a mouse infection model. Consistent with NAD+ regeneration maintaining L. monocytogenes viability and enabling immune evasion, a respiration-deficient strain exhibited elevated bacteriolysis within the host cytosol and NOX rescued this phenotype. These studies show that NAD+ regeneration, rather than oxidative phosphorylation, represents the primary role of L. monocytogenes respiration and highlight the nuanced relationship between bacterial metabolism, physiology, and pathogenesis.

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