scholarly journals Mitochondrial Function and Dysfunction in Dilated Cardiomyopathy

2021 ◽  
Vol 8 ◽  
Author(s):  
Daniela Ramaccini ◽  
Vanessa Montoya-Uribe ◽  
Femke J. Aan ◽  
Lorenzo Modesti ◽  
Yaiza Potes ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Mitochondrial Function ◽  
Reading Ability ◽  
Cardiac Tissue ◽  
Mitochondrial Activity ◽  
Atp Production ◽  
Energy Demands ◽  
Proof Reading ◽  
Mitochondrial Functions ◽  
Optimal Function

Cardiac tissue requires a persistent production of energy in order to exert its pumping function. Therefore, the maintenance of this function relies on mitochondria that represent the “powerhouse” of all cardiac activities. Mitochondria being one of the key players for the proper functioning of the mammalian heart suggests continual regulation and organization. Mitochondria adapt to cellular energy demands via fusion-fission events and, as a proof-reading ability, undergo mitophagy in cases of abnormalities. Ca2+ fluxes play a pivotal role in regulating all mitochondrial functions, including ATP production, metabolism, oxidative stress balance and apoptosis. Communication between mitochondria and others organelles, especially the sarcoplasmic reticulum is required for optimal function. Consequently, abnormal mitochondrial activity results in decreased energy production leading to pathological conditions. In this review, we will describe how mitochondrial function or dysfunction impacts cardiac activities and the development of dilated cardiomyopathy.

scholarly journals Glial Metabolic Reprogramming in Amyotrophic Lateral Sclerosis

2021 ◽  
pp. 1-9
Author(s):  
Patricia Cassina ◽  
Ernesto Miquel ◽  
Laura Martínez-Palma ◽  
Adriana Cassina
Keyword(s):  
Motor Neuron ◽  
Disease Progression ◽  
Glial Cells ◽  
Mitochondrial Function ◽  
Neurodegenerative Disorder ◽  
Metabolic Reprogramming ◽  
Mitochondrial Activity ◽  
Neuron Death ◽  
Energy Demands ◽  
Aberrant Glial Cells

ALS is a human neurodegenerative disorder that induces a progressive paralysis of voluntary muscles due to motor neuron loss. The causes are unknown, and there is no curative treatment available. Mitochondrial dysfunction is a hallmark of ALS pathology; however, it is currently unknown whether it is a cause or a consequence of disease progression. Recent evidence indicates that glial mitochondrial function changes to cope with energy demands and critically influences neuronal death and disease progression. Aberrant glial cells detected in the spinal cord of diseased animals are characterized by increased proliferation rate and reduced mitochondrial bioenergetics. These features can be compared with cancer cell behavior of adapting to nutrient microenvironment by altering energy metabolism, a concept known as metabolic reprogramming. We focus on data that suggest that aberrant glial cells in ALS undergo metabolic reprogramming and profound changes in glial mitochondrial activity, which are associated with motor neuron death in ALS. This review article emphasizes on the association between metabolic reprogramming and glial reactivity, bringing new paradigms from the area of cancer research into neurodegenerative diseases. Targeting glial mitochondrial function and metabolic reprogramming may result in promising therapeutic strategies for ALS.

scholarly journals Protein kinase C-α inhibits the repair of oxidative phosphorylation after S-(1,2-dichlorovinyl)-l-cysteine injury in renal cells

2004 ◽  
Vol 287 (1) ◽  
pp. F64-F73 ◽  
Author(s):  
Xiuli Liu ◽  
Malinda L. Godwin ◽  
Grażyna Nowak
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Oxidative Phosphorylation ◽  
Atpase Activity ◽  
Mitochondrial Function ◽  
Recovery Period ◽  
Β Subunit ◽  
Atp Production ◽  
Kinase C ◽  
Mitochondrial Functions

Previously, we showed that physiological functions of renal proximal tubular cells (RPTC) do not recover following S-(1,2-dichlorovinyl)-l-cysteine (DCVC)-induced injury. This study investigated the role of protein kinase C-α (PKC-α) in the lack of repair of mitochondrial function in DCVC-injured RPTC. After DCVC exposure, basal oxygen consumption (Qo2), uncoupled Qo2, oligomycin-sensitive Qo2, F1F0-ATPase activity, and ATP production decreased, respectively, to 59, 27, 27, 57, and 68% of controls. None of these functions recovered. Mitochondrial transmembrane potential decreased 53% after DCVC injury but recovered on day 4. PKC-α was activated 4.3- and 2.5-fold on days 2 and 4, respectively, of the recovery period. Inhibition of PKC-α activation (10 nM Go6976) did not block DCVC-induced decreases in mitochondrial functions but promoted the recovery of uncoupled Qo2, oligomycin-sensitive Qo2, F1F0-ATPase activity, and ATP production. Protein levels of the catalytic β-subunit of F1F0-ATPase were not changed by DCVC or during the recovery period. Amino acid sequence analysis revealed that α-, β-, and ε-subunits of F1F0-ATPase have PKC consensus motifs. Recombinant PKC-α phosphorylated the β-subunit and decreased F1F0-ATPase activity in vitro. Serine but not threonine phosphorylation of the β-subunit was increased during late recovery following DCVC injury, and inhibition of PKC-α activation decreased this phosphorylation. We conclude that during RPTC recovery following DCVC injury, 1) PKC-α activation decreases F0F1-ATPase activity, oxidative phosphorylation, and ATP production; 2) PKC-α phosphorylates the β-subunit of F1F0-ATPase on serine residue; and 3) PKC-α does not mediate depolarization of RPTC mitochondria. This is the first report showing that PKC-α phosphorylates the catalytic subunit of F1F0-ATPase and that PKC-α plays an important role in regulating repair of mitochondrial function.

Flux-balance analysis of mitochondrial energy metabolism: consequences of systemic stoichiometric constraints

2001 ◽  
Vol 280 (3) ◽  
pp. R695-R704 ◽  
Author(s):  
Ramprasad Ramakrishna ◽  
Jeremy S. Edwards ◽  
Andrew McCulloch ◽  
Bernhard O. Palsson
Keyword(s):  
Flux Balance Analysis ◽  
Mitochondrial Function ◽  
Tca Cycle ◽  
Biochemical Reaction Networks ◽  
Modeling Framework ◽  
Mitochondrial Energy Metabolism ◽  
Atp Production ◽  
Flux Balance ◽  
Mitochondrial Functions ◽  
Balance Analysis

Mitochondrial metabolism is a critical component in the functioning and maintenance of cellular organs. The stoichiometry of biochemical reaction networks imposes constraints on mitochondrial function. A modeling framework, flux-balance analysis (FBA), was used to characterize the optimal flux distributions for maximal ATP production in the mitochondrion. The model predicted the expected ATP yields for glucose, lactate, and palmitate. Genetic defects that affect mitochondrial functions have been implicated in several human diseases. FBA can characterize the metabolic behavior due to genetic deletions at the metabolic level, and the effect of mutations in the tricarboxylic acid (TCA) cycle on mitochondrial ATP production was simulated. The mitochondrial ATP production is severely affected by TCA-cycle mutations. In addition, the model predicts the secretion of TCA-cycle intermediates, which is observed in clinical studies of mitochondriopathies such as those associated with fumarase deficiency. The model provides a systemic perspective to characterize the effect of stoichiometric constraints and specific metabolic fluxes on mitochondrial function.

scholarly journals Palmitate but Not Oleate Exerts a Negative Effect on Oxygen Utilization in Myoblasts of Patients with the m.3243A>G Mutation: A Pilot Study

Life ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 204
Author(s):  
Leila Motlagh Scholle ◽  
Helena Schieffers ◽  
Samiya Al-Robaiy ◽  
Annemarie Thaele ◽  
Diana Lehmann Urban ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Fatty Acids ◽  
Mitochondrial Function ◽  
Stress Responses ◽  
Stress Test ◽  
Saturated Fatty Acids ◽  
Mitochondrial Activity ◽  
Oxygen Utilization ◽  
Atp Production ◽  
Negative Effect

It is known that exposure to excess saturated fatty acids, especially palmitate, can trigger cellular stress responses interpreted as lipotoxicity. The effect of excessive free fatty acids on oxidative phosphorylation capacity in myoblasts of patients with the m.3243A>G mutation was evaluated with the mitochondrial (Mito) stress test using a Seahorse XF96 analyzer. ß-oxidation, measured with the Seahorse XF96 analyzer, was similar in patients and controls, and reduced in both patients and controls at 40 °C compared to 37 °C. Mito stress test in the absence of fatty acids showed lower values in patients compared to controls. The mitochondrial activity and ATP production rates were significantly reduced in presence of palmitate, but not of oleate in patients, showing a negative effect of excessive palmitate on mitochondrial function in patients. Diabetes mellitus is a frequent symptom in patients with m.3243A>G mutation. It can be speculated that the negative effect of palmitate on mitochondrial function might be related to diacylglycerols (DAG) and ceramides (CER) mediated insulin resistance. This might contribute to the elevated risk for diabetes mellitus in m.3243A>G patients.

scholarly journals Mitochondrial Dysfunction in Alzheimer’s Disease: A Biomarker of the Future?

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 63
Author(s):  
Simon M. Bell ◽  
Katy Barnes ◽  
Matteo De Marco ◽  
Pamela J. Shaw ◽  
Laura Ferraiuolo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Function ◽  
Imaging Techniques ◽  
The Body ◽  
Atp Production ◽  
Disease Modifying Therapies ◽  
Mitochondrial Functions ◽  
Species Production ◽  
The Brain

Alzheimer’s disease (AD) is the most common cause of dementia worldwide and is characterised pathologically by the accumulation of amyloid beta and tau protein aggregates. Currently, there are no approved disease modifying therapies for clearance of either of these proteins from the brain of people with AD. As well as abnormalities in protein aggregation, other pathological changes are seen in this condition. The function of mitochondria in both the nervous system and rest of the body is altered early in this disease, and both amyloid and tau have detrimental effects on mitochondrial function. In this review article, we describe how the function and structure of mitochondria change in AD. This review summarises current imaging techniques that use surrogate markers of mitochondrial function in both research and clinical practice, but also how mitochondrial functions such as ATP production, calcium homeostasis, mitophagy and reactive oxygen species production are affected in AD mitochondria. The evidence reviewed suggests that the measurement of mitochondrial function may be developed into a future biomarker for early AD. Further work with larger cohorts of patients is needed before mitochondrial functional biomarkers are ready for clinical use.

scholarly journals Reg3g ameliorates Tacrolimus-induced pancreatic β cell dysfunction by restoring mitochondrial function

2021 ◽  
Author(s):  
Ming Xiang ◽  
Senlin Li ◽  
Hong Zhou ◽  
Mengyuan Xie ◽  
Zijun Zhang ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Calcium Uptake ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Atp Production ◽  
Mitochondria Membrane Potential ◽  
Cell Dysfunction ◽  
Mitochondrial Functions ◽  
Induced Apoptosis

Background and Purpose: Tacrolimus (Tac) induces pancreatic β cell dysfunction, causing new-onset diabetes mellitus (NODM) after transplantation. Reg3g is a member of the pancreatic regenerative gene family, as reported to improve type 1 diabetes by promoting β cell regeneration. Here, we aim to investigate the role and approach of Reg3g in reversing Tac-induced β cell dysfunction and NODM in mice. Experimental Approach: Circulating REG3A (the human homolog of mouse Reg3g) concentrations of patients treated with Tac after heart transplantation(HT) were detected. The glucose-stimulated insulin secretion (GSIS) and mitochondrial functions, including mitochondria membrane potential (MMP), mitochondria calcium uptake, ATP production, and oxygen consumption rate (OCR), were tested in β cells. Effects of Reg3g on Tac-induced NODM in mice were studied. Key Results: Circulating REG3A levels significantly decreased in NODM patients treated with Tac compared with those without diabetes. Tac down-regulated Reg3g via inhibiting STAT3-mediated transcription activation, while Reg3g protected against Tac-induced apoptosis of β cells. Besides, Reg3g restored GSIS suppressed by Tac in β cells via improving mitochondrial function, including increased MMP, mitochondria calcium uptake, ATP production, and OCR. Mechanically, Reg3g increased accumulation of pSTAT3(Ser727) in mitochondria by activating ERK1/2-STAT3 signaling pathway, leading to restoration of Tac-caused mitochondrial impairment. Moreover, Reg3g overexpression effectively ameliorated Tac-induced NODM in mice. Conclusion and Implications: Reg3g ameliorates Tac-induced pancreatic β cell dysfunction by restoring mitochondrial function via a pSTAT3(Ser727)-dependent way. Our observations identify a novel Reg3g-involved mechanism underlying the augmented incidence of Tac-induced NODM and reveal that Reg3g ameliorates Tac-induced β cell dysfunction.

scholarly journals AP39, a Mitochondria-Targeted Hydrogen Sulfide Donor, Supports Cellular Bioenergetics and Protects against Alzheimer’s Disease by Preserving Mitochondrial Function in APP/PS1 Mice and Neurons

2016 ◽  
Vol 2016 ◽  
pp. 1-19 ◽  
Author(s):  
Feng-li Zhao ◽  
Fang Fang ◽  
Pei-feng Qiao ◽  
Ning Yan ◽  
Dan Gao ◽  
...  
Keyword(s):  
Cell Viability ◽  
Mitochondrial Function ◽  
Mitochondrial Dynamics ◽  
Drug Candidate ◽  
Mitochondrial Activity ◽  
Ros Generation ◽  
High Concentration ◽  
Low Concentrations ◽  
Mitochondrial Functions ◽  
Cellular Bioenergetics

Increasing evidence suggests that mitochondrial functions are altered in AD and play an important role in AD pathogenesis. It has been established that H2S homeostasis is balanced in AD. The emerging mitochondrial roles of H2S include antioxidation, antiapoptosis, and the modulation of cellular bioenergetics. Here, using primary neurons from the well-characterized APP/PS1 transgenic mouse model, we studied the effects of AP39 (a newly synthesized mitochondrially targeted H2S donor) on mitochondrial function. AP39 increased intracellular H2S levels, mainly in mitochondrial regions. AP39 exerted dose-dependent effects on mitochondrial activity in APP/PS1 neurons, including increased cellular bioenergy metabolism and cell viability at low concentrations (25–100 nM) and decreased energy production and cell viability at a high concentration (250 nM). Furthermore, AP39 (100 nM) increased ATP levels, protected mitochondrial DNA, and decreased ROS generation. AP39 regulated mitochondrial dynamics, shifting from fission toward fusion. After 6 weeks, AP39 administration to APP/PS1 mice significantly ameliorated their spatial memory deficits in the Morris water maze and NORT and reduced Aβdeposition in their brains. Additionally, AP39 inhibited brain atrophy in APP/PS1 mice. Based on these results, AP39 was proposed as a promising drug candidate for AD treatment, and its anti-AD mechanism may involve protection against mitochondrial damage.

scholarly journals Metabolic Remodeling and Implicated Calcium and Signal Transduction Pathways in the Pathogenesis of Heart Failure

2021 ◽  
Vol 22 (19) ◽  
pp. 10579
Author(s):  
Antoine H. Chaanine
Keyword(s):  
Heart Failure ◽  
Signaling Pathways ◽  
Mitochondrial Function ◽  
Molecular Mechanisms ◽  
High Energy ◽  
Atp Production ◽  
Cellular Survival ◽  
Energy Demands ◽  
Metabolic Remodeling ◽  
Close Proximity

The heart is an organ with high-energy demands in which the mitochondria are most abundant. They are considered the powerhouse of the cell and occupy a central role in cellular metabolism. The intermyofibrillar mitochondria constitute the majority of the three-mitochondrial subpopulations in the heart. They are also considered to be the most important in terms of their ability to participate in calcium and cellular signaling, which are critical for the regulation of mitochondrial function and adenosine triphosphate (ATP) production. This is because they are located in very close proximity with the endoplasmic reticulum (ER), and for the presence of tethering complexes enabling interorganelle crosstalk via calcium signaling. Calcium is an important second messenger that regulates mitochondrial function. It promotes ATP production and cellular survival under physiological changes in cardiac energetic demand. This is accomplished in concert with signaling pathways that regulate both calcium cycling and mitochondrial function. Perturbations in mitochondrial homeostasis and metabolic remodeling occupy a central role in the pathogenesis of heart failure. In this review we will discuss perturbations in ER-mitochondrial crosstalk and touch on important signaling pathways and molecular mechanisms involved in the dysregulation of calcium homeostasis and mitochondrial function in heart failure.

scholarly journals Long-Term Caffeine Intake Exerts Protective Effects on Intestinal Aging by Regulating Vitellogenesis and Mitochondrial Function in an Aged Caenorhabditis Elegans Model

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2517
Author(s):  
Hyemin Min ◽  
Esther Youn ◽  
Yhong-Hee Shim
Keyword(s):  
Caenorhabditis Elegans ◽  
Mitochondrial Function ◽  
Biological Activities ◽  
Caffeine Intake ◽  
Mitochondrial Activity ◽  
Protective Effects ◽  
Aging Effects ◽  
Mitochondrial Functions ◽  
Antioxidant Proteins

Caffeine, a methylxanthine derived from plants, is the most widely consumed ingredient in daily life. Therefore, it is necessary to investigate the effects of caffeine intake on essential biological activities. In this study, we attempted to determine the possible anti-aging effects of long-term caffeine intake in the intestine of an aged Caenorhabditis elegans model. We examined changes in intestinal integrity, production of vitellogenin (VIT), and mitochondrial function after caffeine intake. To evaluate intestinal aging, actin-5 (ACT-5) mislocalization, lumenal expansion, and intestinal colonization were examined after caffeine intake, and the levels of vitellogenesis as well as the mitochondrial activity were measured. We found that the long-term caffeine intake (10 mM) in the L4-stage worms at 25 °C for 3 days suppressed ACT-5 mislocalization. Furthermore, the level of autophagy, which is normally increased in aging animals, was significantly reduced in these animals, and their mitochondrial functions improved after caffeine intake. In addition, the caffeine-ingesting aging animals showed high resistance to oxidative stress and increased the expression of antioxidant proteins. Taken together, these findings reveal that caffeine may be a potential anti-aging agent that can suppress intestinal atrophy during the progression of intestinal aging.

Schisandrin Restores the Amyloid β-Induced Impairments on Mitochondrial Function, Energy Metabolism, Biogenesis, and Dynamics in Rat Primary Hippocampal Neurons

Pharmacology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Zhongyuan Piao ◽  
Lin Song ◽  
Lifen Yao ◽  
Limei Zhang ◽  
Yichan Lu
Keyword(s):  
Energy Metabolism ◽  
Cytochrome C ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Hippocampal Neurons ◽  
Citrate Synthase ◽  
Mitochondrial Permeability Transition ◽  
Amyloid Β ◽  
Mitochondrial Functions ◽  
Primary Hippocampal Neurons

Introduction: Schisandrin which is derived from Schisandra chinensis has shown multiple pharmacological effects on various diseases including Alzheimer’s disease (AD). It is demonstrated that mitochondrial dysfunction plays an essential role in the pathogenesis of neurodegenerative disorders. Objective: Our study aims to investigate the effects of schisandrin on mitochondrial functions and metabolisms in primary hippocampal neurons. Methods: In our study, rat primary hippocampal neurons were isolated and treated with indicated dose of amyloid β1–42 (Aβ1–42) oligomer to establish a cell model of AD in vitro. Schisandrin (2 μg/mL) was further subjected to test its effects on mitochondrial function, energy metabolism, mitochondrial biogenesis, and dynamics in the Aβ1–42 oligomer-treated neurons. Results and Conclusions: Our findings indicated that schisandrin significantly alleviated the Aβ1–42 oligomer-induced loss of mitochondrial membrane potential and impaired cytochrome c oxidase activity. Additionally, the opening of mitochondrial permeability transition pore and release of cytochrome c were highly restricted with schisandrin treatment. Alterations in cell viability, ATP production, citrate synthase activity, and the expressions of glycolysis-related enzymes demonstrated the relief of defective energy metabolism in Aβ-treated neurons after the treatment of schisandrin. For mitochondrial biogenesis, elevated expression of peroxisome proliferator-activated receptor γ coactivator along with promoted mitochondrial mass was found in schisandrin-treated cells. The imbalance in the cycle of fusion and fission was also remarkably restored by schisandrin. In summary, this study provides novel mechanisms for the protective effect of schisandrin on mitochondria-related functions.

Sign in / Sign up

Export Citation Format

Share Document