Mitochondrial Ion Channels in Cardiac Function

2021 ◽  
Author(s):  
Harpreet Singh
Keyword(s):  
Ion Channels ◽  
Cardiac Function ◽  
Mitochondrial Dysfunction ◽  
Oxidative Metabolism ◽  
High Energy ◽  
Main Function ◽  
Mitochondrial Membranes ◽  
Inner Mitochondrial Membrane ◽  
Ionic Homeostasis ◽  
Energy Demands

Mitochondria have been recognized as key organelles in cardiac physiology and are potential targets for clinical interventions to improve cardiac function. Mitochondrial dysfunction has been accepted as a major contributor to the development of heart failure. The main function of mitochondria is to meet the high energy demands of the heart by oxidative metabolism. Ionic homeostasis in mitochondria directly regulates oxidative metabolism, and any disruption in ionic homeostasis causes mitochondrial dysfunction and eventually contractile failure. The mitochondrial ionic homeostasis is closely coupled with inner mitochondrial membrane potential. To regulate and maintain ionic homeostasis, mitochondrial membranes are equipped with ion transporting proteins. Ion transport mechanisms involving several different ion channels and transporters are highly efficient and dynamic, thus helping to maintain the ionic homeostasis of ions as well as their salts present in the mitochondrial matrix. In recent years, several novel proteins have been identified on the mitochondrial membranes and these proteins are actively being pursued in research for roles in the organ as well as organelle physiology. In this article, the role of mitochondrial ion channels in cardiac function is reviewed. In recent times, the major focus of the mitochondrial ion channel field is to establish molecular identities as well as assigning specific functions to them. Given the diversity of mitochondrial ion channels and their unique roles in cardiac function, they present novel and viable therapeutic targets for cardiac diseases.

scholarly journals Mitochondrial dysfunction and energy deprivation in the mechanism of neurodegeneration

2019 ◽  
Vol 44 (6) ◽  
pp. 723-729 ◽  
Author(s):  
Andrey Y. Abramov ◽  
Plamena R. Angelova
Keyword(s):  
Mitochondrial Dysfunction ◽  
Mitochondrial Dynamics ◽  
Neuronal Loss ◽  
High Energy ◽  
Neuronal Function ◽  
Cellular Functions ◽  
Energy Demands ◽  
Mitochondrial Toxins ◽  
Energy Deprivation ◽  
Species Production

Abstract Energy-producing organelles mitochondria are involved in a number of cellular functions. Deregulation of mitochondrial function due to mutations or effects of mitochondrial toxins is proven to be a trigger for diverse pathologies, including neurodegenerative disorders. Despite the extensive research done in the last decades, the mechanisms by which mitochondrial dysfunction leads to neuronal deregulation and cell death have not yet been fully elucidated. Brain cells are specifically dependent on mitochondria due to their high energy demands to maintain neuronal ion gradients and signal transduction, and also, to mediate neuronal health through the processes of mitochondrial calcium homeostasis, mitophagy, mitochondrial reactive oxygen species production and mitochondrial dynamics. Some of these processes have been independently implicated in the mechanism of neuronal loss in neurodegeneration. Moreover, it is increasingly recognised that these processes are interdependent and interact within the mitochondria to ensure proper neuronal function and survival.

scholarly journals The Role of the Antioxidant Response in Mitochondrial Dysfunction in Degenerative Diseases: Cross-Talk between Antioxidant Defense, Autophagy, and Apoptosis

2019 ◽  
Vol 2019 ◽  
pp. 1-26 ◽  
Author(s):  
Michael L.-H. Huang ◽  
Shannon Chiang ◽  
Danuta S. Kalinowski ◽  
Dong-Hun Bae ◽  
Sumit Sahni ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Dynamics ◽  
Signal Transmission ◽  
Antioxidant Response ◽  
High Energy ◽  
Stress Factors ◽  
Degenerative Diseases ◽  
Energy Demands ◽  
Stress Energy

The mitochondrion is an essential organelle important for the generation of ATP for cellular function. This is especially critical for cells with high energy demands, such as neurons for signal transmission and cardiomyocytes for the continuous mechanical work of the heart. However, deleterious reactive oxygen species are generated as a result of mitochondrial electron transport, requiring a rigorous activation of antioxidative defense in order to maintain homeostatic mitochondrial function. Indeed, recent studies have demonstrated that the dysregulation of antioxidant response leads to mitochondrial dysfunction in human degenerative diseases affecting the nervous system and the heart. In this review, we outline and discuss the mitochondrial and oxidative stress factors causing degenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Friedreich’s ataxia. In particular, the pathological involvement of mitochondrial dysfunction in relation to oxidative stress, energy metabolism, mitochondrial dynamics, and cell death will be explored. Understanding the pathology and the development of these diseases has highlighted novel regulators in the homeostatic maintenance of mitochondria. Importantly, this offers potential therapeutic targets in the development of future treatments for these degenerative diseases.

Enzyme activity changes in rat soleus motoneurons and muscle after synergist ablation

1987 ◽  
Vol 63 (6) ◽  
pp. 2301-2308 ◽  
Author(s):  
J. K. Pearson ◽  
D. W. Sickles
Keyword(s):  
Enzyme Activity ◽  
Oxidative Metabolism ◽  
Muscle Fibers ◽  
High Energy ◽  
Glycolytic Enzyme ◽  
Short Term ◽  
Glycerophosphate Dehydrogenase ◽  
Energy Demands ◽  
Tight Correlation ◽  
Fast Twitch

Quantitative enzyme histochemical methods have been used to determine the effect of ablation of synergists on the oxidative metabolism of the alpha-motoneurons and muscle fibers of the rat soleus. Sixty days postablation, the NADH-tetrazolium reductase (NADH-TR) activity of soleus motoneurons decreased 12.5% from 0.327 +/- 0.005 (mean +/- SE; optical density units) to 0.286 +/- 0.007. In the muscle fibers, the alpha-glycerophosphate dehydrogenase activity (glycolytic enzyme) decreased from 0.114 +/- 0.010 to 0.074 +/- 0.009, a change of 35.1%, and the NADH-TR activity decreased 21.2% from 0.348 +/- 0.018 to 0.274 +/- 0.017. In both the motoneurons and the muscle fibers, the decrease was nonspecific for all cells, although a greater effect on the cells with higher enzyme activity was observed. The decreased NADH-TR activity represents a shift in the oxidative profile of the motoneurons and muscle fibers, indicating a decreased ability to use oxidative metabolism for periods of short-term high-energy demands. Furthermore, the parallel decrease in muscle fibers and motoneurons with high NADH-TR activity (fast-twitch oxidative-glycolytic fibers and presumably also motoneurons) demonstrates the tight correlation of the NADH-TR activity between these parts of the motor unit in both control and synergist-ablated muscles.

scholarly journals Effect of defibrillation on the performance of an implantable vagus nerve stimulation system

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Imad Libbus ◽  
Scott R. Stubbs ◽  
Scott T. Mazar ◽  
Scott Mindrebo ◽  
Bruce H. KenKnight ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Pulse Generator ◽  
High Energy ◽  
Implantable Pulse Generator ◽  
Defibrillation Pulse ◽  
Stimulation System

Abstract Background Vagus Nerve Stimulation (VNS) delivers Autonomic Regulation Therapy (ART) for heart failure (HF), and has been associated with improvement in cardiac function and heart failure symptoms. VNS is delivered using an implantable pulse generator (IPG) and lead with electrodes placed around the cervical vagus nerve. Because HF patients may receive concomitant cardiac defibrillation therapy, testing was conducted to determine the effect of defibrillation (DF) on the VNS system. Methods DF testing was conducted on three ART IPGs (LivaNova USA, Inc.) according to international standard ISO14708-1, which evaluated whether DF had any permanent effects on the system. Each IPG was connected to a defibrillation pulse generator and subjected to a series of high-energy pulses. Results The specified series of pulses were successfully delivered to each of the three devices. All three IPGs passed factory electrical tests, and interrogation confirmed that software and data were unchanged from the pre-programmed values. No shifts in parameters or failures were observed. Conclusions Implantable VNS systems were tested for immunity to defibrillation, and were found to be unaffected by a series of high-energy defibrillation pulses. These results suggest that this VNS system can be used safely and continue to function after patients have been defibrillated.

scholarly journals The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 489
Author(s):  
Hilary Y. Liu ◽  
Jenna R. Gale ◽  
Ian J. Reynolds ◽  
John H. Weiss ◽  
Elias Aizenman
Keyword(s):  
Mitochondrial Permeability Transition ◽  
Neuronal Damage ◽  
Mitochondrial Fission ◽  
Permeability Transition ◽  
High Energy ◽  
Atp Depletion ◽  
Ros Generation ◽  
Cellular Functions ◽  
Calcium Deregulation ◽  
Energy Demands

Zinc is a highly abundant cation in the brain, essential for cellular functions, including transcription, enzymatic activity, and cell signaling. However, zinc can also trigger injurious cascades in neurons, contributing to the pathology of neurodegenerative diseases. Mitochondria, critical for meeting the high energy demands of the central nervous system (CNS), are a principal target of the deleterious actions of zinc. An increasing body of work suggests that intracellular zinc can, under certain circumstances, contribute to neuronal damage by inhibiting mitochondrial energy processes, including dissipation of the mitochondrial membrane potential (MMP), leading to ATP depletion. Additional consequences of zinc-mediated mitochondrial damage include reactive oxygen species (ROS) generation, mitochondrial permeability transition, and excitotoxic calcium deregulation. Zinc can also induce mitochondrial fission, resulting in mitochondrial fragmentation, as well as inhibition of mitochondrial motility. Here, we review the known mechanisms responsible for the deleterious actions of zinc on the organelle, within the context of neuronal injury associated with neurodegenerative processes. Elucidating the critical contributions of zinc-induced mitochondrial defects to neurotoxicity and neurodegeneration may provide insight into novel therapeutic targets in the clinical setting.

scholarly journals Processing Methodologies of Wet Microalga Biomass Toward Oil Separation: An Overview

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 641
Author(s):  
Vânia Pôjo ◽  
Tânia Tavares ◽  
Francisco Xavier Malcata
Keyword(s):  
Food System ◽  
Lipid Extraction ◽  
High Energy ◽  
Economic Feasibility ◽  
Alternative Source ◽  
Microalgal Biomass ◽  
Energy Demands ◽  
Chemical Profiles ◽  
System Sustainability ◽  
Industrial Level

One of the main goals of Mankind is to ensure food system sustainability—including management of land, soil, water, and biodiversity. Microalgae accordingly appear as an innovative and scalable alternative source in view of the richness of their chemical profiles. In what concerns lipids in particular, microalgae can synthesize and accumulate significant amounts of fatty acids, a great fraction of which are polyunsaturated; this makes them excellent candidates within the framework of production and exploitation of lipids by various industrial and health sectors, either as bulk products or fine chemicals. Conventional lipid extraction methodologies require previous dehydration of microalgal biomass, which hampers economic feasibility due to the high energy demands thereof. Therefore, extraction of lipids directly from wet biomass would be a plus in this endeavor. Supporting processes and methodologies are still limited, and most approaches are empirical in nature—so a deeper mechanistic elucidation is a must, in order to facilitate rational optimization of the extraction processes. Besides circumventing the current high energy demands by dehydration, an ideal extraction method should be selective, sustainable, efficient, harmless, and feasible for upscale to industrial level. This review presents and discusses several pretreatments incurred in lipid extraction from wet microalga biomass, namely recent developments and integrated processes. Unfortunately, most such developments have been proven at bench-scale only—so demonstration in large facilities is still needed to confirm whether they can turn into competitive alternatives.

GESTATIONAL DIABETES PROGRAMS MITOCHONDRIAL DYSFUNCTION AND IMPAIRS CARDIAC FUNCTION IN THE OFFSPRING

2016 ◽  
Vol 32 (10) ◽  
pp. S82-S83
Author(s):  
S.M. Kereliuk ◽  
K.G. Cheung ◽  
B. Xiang ◽  
L.K. Cole ◽  
T.J. Pereira ◽  
...  
Keyword(s):  
Gestational Diabetes ◽  
Cardiac Function ◽  
Mitochondrial Dysfunction

Seasonal and daily activity patterns in a Canadian population of the prairie rattlesnake, Crotalus viridus viridis

1985 ◽  
Vol 63 (1) ◽  
pp. 86-91 ◽  
Author(s):  
V. P. J. Gannon ◽  
D. M. Secoy
Keyword(s):  
Daily Activity ◽  
Activity Patterns ◽  
High Energy ◽  
Time Of Day ◽  
Energy Demands ◽  
Level Of Activity ◽  
Canadian Population ◽  
Significant Difference ◽  
Gravid Females ◽  
Daily Activity Patterns

The seasonal and daily activity patterns of a Saskatchewan population of Crotalus viridus viridis is presented. Snakes emerged from hibernation in late April and migrated into the surrounding river valley and upland regions in early May. Adult migration preceded that of immature age-classes. Several gravid females occupied a rookery near the hibernaculum during the summer months and remained there until parturition. Females did not occupy this site in successive years and may have a biennial or greater reproductive cycle. Snakes returned to the hibernaculum in early September and remained active until early October. The behaviour of snakes in a field enclosure in response to time of day and body temperature (Tb) was recorded during the spring, summer, and fall. Significant differences in the Tb values of sunning, movement, and shading behaviours were noted. Gravid females were significantly more active in all seasons. However, no significant difference in mean Tb was found between males and females in the field, enclosure study, or laboratory thermal gradient. The observed greater level of activity may reflect the high energy demands of gravid females.

Reduced high-energy phosphate levels in rat hearts. I. Effects of alloxan diabetes

1976 ◽  
Vol 230 (6) ◽  
pp. 1744-1750 ◽  
Author(s):  
TB Allison ◽  
SP Bruttig ◽  
Crass MF ◽  
RS Eliot ◽  
JC Shipp
Keyword(s):  
Oxidative Metabolism ◽  
Oxygen Delivery ◽  
Rat Heart ◽  
High Energy ◽  
Diabetic Rat ◽  
High Energy Phosphate ◽  
Atp Production ◽  
Rat Hearts

Significant alterations in heart carbohydrate and lipid metabolism are present 48 h after intravenous injection of alloxan (60 mg/kg) in rats. It has been suggested that uncoupling of oxidative phosphorylation occurs in the alloxanized rat heart in vivo, whereas normal oxidative metabolism has been demonstrated in alloxan-diabetic rat hearts perfused in vitro under conditions of adequate oxygen delivery. We examined the hypothesis that high-energy phosphate metabolism might be adversely affected in the alloxan-diabetic rat heart in vivo. Phosphocreatine and ATP were reduced by 58 and 45%, respectively (P is less than 0.001). Also, oxygen-dissociation curves were shifted to the left by 4 mmHg, and the rate of oxygen release from blood was reduced by 21% (P is less than 0.01). Insulin administration normalized heart high-energy phosphate compounds. ATP production was accelerated in diabetic hearts perfused in vitro with a well-oxygenated buffer. These studies support the hypothesis that oxidative ATP production in the alloxan-diabetic rat heart is reduced and suggest that decreased oxygen delivery may have a regulatory role in the oxidative metabolism of the diabetic rat heart.

scholarly journals Metabolic features of mouse and human retinas: rods vs. cones, macula vs. periphery, retina vs. RPE

2020 ◽  
Author(s):  
Bo Li ◽  
Ting Zhang ◽  
Wei Liu ◽  
Yekai Wang ◽  
Rong Xu ◽  
...  
Keyword(s):  
Aerobic Glycolysis ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Lipid Synthesis ◽  
Metabolic Stress ◽  
Tca Cycle ◽  
High Energy ◽  
Metabolic Dysfunction ◽  
Metabolic Demand ◽  
Energy Demands

AbstractPhotoreceptors, especially cones, which are enriched in the human macula, have high energy demands, making them vulnerable to metabolic stress. Metabolic dysfunction of photoreceptors and their supporting retinal pigment epithelium (RPE) is an important underlying cause of degenerative retinal diseases. However, how cones and the macula support their exorbitant metabolic demand and communicate with RPE is unclear. By profiling metabolite uptake and release and analyzing metabolic genes, we have found cone-rich retinas and human macula share specific metabolic features with upregulated pathways in pyruvate metabolism, mitochondrial TCA cycle and lipid synthesis. Human neural retina and RPE have distinct but complementary metabolic features. Retinal metabolism centers on NADH production and neurotransmitter biosynthesis. The retina needs aspartate to sustain its aerobic glycolysis and mitochondrial metabolism. RPE metabolism is directed toward NADPH production and biosynthesis of acetyl-rich metabolites, serine and others. RPE consumes multiple nutrients, including proline, to produce metabolites for the retina.

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