scholarly journals Cytosolic, but not matrix, calcium is essential for adjustment of mitochondrial pyruvate supply

2020 ◽  
Vol 295 (14) ◽  
pp. 4383-4397 ◽  
Author(s):  
Marten Szibor ◽  
Zemfira Gizatullina ◽  
Timur Gainutdinov ◽  
Thomas Endres ◽  
Grazyna Debska-Vielhaber ◽  
...  
Keyword(s):  
Oxidation Reaction ◽  
Control Mechanisms ◽  
Mitochondrial Matrix ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Phenotypic Changes ◽  
Substrate Supply ◽  
Health And Disease ◽  
Malate Aspartate Shuttle ◽  
Working Rat Heart

Mitochondrial oxidative phosphorylation (OXPHOS) and cellular workload are tightly balanced by the key cellular regulator, calcium (Ca2+). Current models assume that cytosolic Ca2+ regulates workload and that mitochondrial Ca2+ uptake precedes activation of matrix dehydrogenases, thereby matching OXPHOS substrate supply to ATP demand. Surprisingly, knockout (KO) of the mitochondrial Ca2+ uniporter (MCU) in mice results in only minimal phenotypic changes and does not alter OXPHOS. This implies that adaptive activation of mitochondrial dehydrogenases by intramitochondrial Ca2+ cannot be the exclusive mechanism for OXPHOS control. We hypothesized that cytosolic Ca2+, but not mitochondrial matrix Ca2+, may adapt OXPHOS to workload by adjusting the rate of pyruvate supply from the cytosol to the mitochondria. Here, we studied the role of malate-aspartate shuttle (MAS)-dependent substrate supply in OXPHOS responses to changing Ca2+ concentrations in isolated brain and heart mitochondria, synaptosomes, fibroblasts, and thymocytes from WT and MCU KO mice and the isolated working rat heart. Our results indicate that extramitochondrial Ca2+ controls up to 85% of maximal pyruvate-driven OXPHOS rates, mediated by the activity of the complete MAS, and that intramitochondrial Ca2+ accounts for the remaining 15%. Of note, the complete MAS, as applied here, included besides its classical NADH oxidation reaction the generation of cytosolic pyruvate. Part of this largely neglected mechanism has previously been described as the “mitochondrial gas pedal.” Its implementation into OXPHOS control models integrates seemingly contradictory results and warrants a critical reappraisal of metabolic control mechanisms in health and disease.

Mitochondrial matrix calcium ions regulate energy production in myocardium: A cytochemical study

1990 ◽  
Vol 48 (2) ◽  
pp. 166-167
Author(s):  
W.A. Jacob ◽  
R. Hertsens ◽  
A. Van Bogaert ◽  
M. De Smet
Keyword(s):  
Energy Metabolism ◽  
Calcium Ions ◽  
Energy Production ◽  
Regulation Of Respiration ◽  
Free Calcium ◽  
Mitochondrial Matrix ◽  
Cytochemical Study ◽  
Nmr Techniques

In the past most studies of the control of energy metabolism focus on the role of the phosphorylation potential ATP/ADP.Pi on the regulation of respiration. Studies using NMR techniques have demonstrated that the concentrations of these compounds for oxidation phosphorylation do not change appreciably throughout the cardiac cycle and during increases in cardiac work. Hence regulation of energy production by calcium ions, present in the mitochondrial matrix, has been the object of a number of recent studies.Three exclusively intramitochondnal dehydrogenases are key enzymes for the regulation of oxidative metabolism. They are activated by calcium ions in the low micromolar range. Since, however, earlier estimates of the intramitochondnal calcium, based on equilibrium thermodynamic considerations, were in the millimolar range, a physiological correlation was not evident. The introduction of calcium-sensitive probes fura-2 and indo-1 made monitoring of free calcium during changing energy metabolism possible. These studies were performed on isolated mitochondria and extrapolation to the in vivo situation is more or less speculative.

scholarly journals Using Regulatory Flexibility to Address Market Informality in Seed Systems: A Global Study

Agronomy ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 377
Author(s):  
Katrin Kuhlmann ◽  
Bhramar Dey
Keyword(s):  
Seed Quality ◽  
Regulatory Environment ◽  
Control Mechanisms ◽  
Seed Systems ◽  
High Quality ◽  
Design And Implementation ◽  
Key Dimensions ◽  
Regulatory Flexibility

Seed rules and regulations determine who can produce and sell seeds, which varieties will be available in the market, the quality of seed for sale, and where seed can be bought and sold. The legal and regulatory environment for seed impacts all stakeholders, including those in the informal sector, through shaping who can participate in the market and the quality and diversity of seed available. This paper addresses a gap in the current literature regarding the role of law and regulation in linking the informal and formal seed sectors and creating more inclusive and better governed seed systems. Drawing upon insights from the literature, global case studies, key expert consultations, and a methodology on the design and implementation of law and regulation, we present a framework that evaluates how regulatory flexibility can be built into seed systems to address farmers’ needs and engage stakeholders of all sizes. Our study focuses on two key dimensions: extending market frontiers and liberalizing seed quality control mechanisms. We find that flexible regulatory approaches and practices play a central role in building bridges between formal and informal seed systems, guaranteeing quality seed in the market, and encouraging market entry for high-quality traditional and farmer-preferred varieties.

scholarly journals Chromosome Instability, Aging and Brain Diseases

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1256
Author(s):  
Ivan Y. Iourov ◽  
Yuri B. Yurov ◽  
Svetlana G. Vorsanova ◽  
Sergei I. Kutsev
Keyword(s):  
Brain Aging ◽  
Chromosome Instability ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Accelerated Aging ◽  
Brain Diseases ◽  
Aging Brain ◽  
Ontogenetic Changes ◽  
Health And Disease

Chromosome instability (CIN) has been repeatedly associated with aging and progeroid phenotypes. Moreover, brain-specific CIN seems to be an important element of pathogenic cascades leading to neurodegeneration in late adulthood. Alternatively, CIN and aneuploidy (chromosomal loss/gain) syndromes exhibit accelerated aging phenotypes. Molecularly, cellular senescence, which seems to be mediated by CIN and aneuploidy, is likely to contribute to brain aging in health and disease. However, there is no consensus about the occurrence of CIN in the aging brain. As a result, the role of CIN/somatic aneuploidy in normal and pathological brain aging is a matter of debate. Still, taking into account the effects of CIN on cellular homeostasis, the possibility of involvement in brain aging is highly likely. More importantly, the CIN contribution to neuronal cell death may be responsible for neurodegeneration and the aging-related deterioration of the brain. The loss of CIN-affected neurons probably underlies the contradiction between reports addressing ontogenetic changes of karyotypes within the aged brain. In future studies, the combination of single-cell visualization and whole-genome techniques with systems biology methods would certainly define the intrinsic role of CIN in the aging of the normal and diseased brain.

scholarly journals The Role of Cell Metabolism in Innate Immune Memory

2020 ◽  
pp. 1-9
Author(s):  
Anaisa Valido Ferreira ◽  
Jorge Domiguéz-Andrés ◽  
Mihai Gheorghe Netea
Keyword(s):  
Metabolic Pathways ◽  
Tricarboxylic Acid Cycle ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Immune Memory ◽  
Functional Changes ◽  
Trained Immunity ◽  
Health And Disease

Immunological memory is classically attributed to adaptive immune responses, but recent studies have shown that challenged innate immune cells can display long-term functional changes that increase nonspecific responsiveness to subsequent infections. This phenomenon, coined <i>trained immunity</i> or <i>innate immune memory</i>, is based on the epigenetic reprogramming and the rewiring of intracellular metabolic pathways. Here, we review the different metabolic pathways that are modulated in trained immunity. Glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, amino acid, and lipid metabolism are interplaying pathways that are crucial for the establishment of innate immune memory. Unraveling this metabolic wiring allows for a better understanding of innate immune contribution to health and disease. These insights may open avenues for the development of future therapies that aim to harness or dampen the power of the innate immune response.

Compensation Control Mechanisms in the American States

1989 ◽  
Vol 18 (3) ◽  
pp. 325-338 ◽  
Author(s):  
Wendell C. Lawther ◽  
Earle C. Traynham ◽  
Kenneth M. Jennings
Keyword(s):  
Collective Bargaining ◽  
State Government ◽  
Control Mechanisms ◽  
Compensation Control ◽  
Initial Analysis ◽  
Personnel Practices ◽  
State Compensation ◽  
American States

There are few studies which report on the personnel practices in the American states. A survey of state compensation analysts in the Summer of 1987 elicited information concerning the use of compensation controls in state government. Results indicate that with the exception of wage and salary surveys, data concerning compensation controls is rarely collected. Initial analysis indicates that the role of the legislature and the existence of collective bargaining may have an impact on the number of controls used.

scholarly journals Dynamics of Oxidation of Reduced Forms of CO2 under Electrochemical and Open-Сircuit Conditions on Polycrystalline Pt in H2CO3

Metals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 274
Author(s):  
Alexander V. Smolin ◽  
Мikhail N. Mikhailov ◽  
Aleksey F. Gadzaov ◽  
Leonid M. Kustov
Keyword(s):  
Quantum Chemical ◽  
Preliminary Analysis ◽  
Oxidation Reaction ◽  
Density Functional ◽  
Oxidation Process ◽  
Open Circuit ◽  
Organic Substances ◽  
Oxidation Of Co ◽  
Reduced Forms

The problem of identifying correlations between catalytic and electrocatalytic processes is one of the fundamental problems of catalysis among “simple” organic substances, and the oxidation of CO and rCO2 is of great interest, since CO and CO2 are considered in pairs both during catalytic and electrocatalytic transformations. In the case of electrocatalysis, this analysis is important in the study of fuel cells. In this paper, we studied the correlation between the oxidation of reduced forms of CO2 (rCO2) under potentiodynamic-galvanoctatic electrochemical and open-circuit conditions of measurements on polycrystalline (pc)Pt in H2CO3. Periodic oscillations are revealed at the oxidation of Had and rCO2 on (pc)Pt. Quantum chemical calculations were carried out on the Pt13 cluster in order to identify the mechanisms of the rCO2 oxidation reaction. The correspondence in the energy parameters of the oxidation process of rCO2 under open-circuit conditions and electrochemical conditions is shown. The preliminary analysis of the system using density functional (DFT) calculations is carried out and the most stable systems that are based on Pt13 are found, namely rOH-Pt13-(CO)n, rOH-Pt13-(COH) and rOH-Pt13-(rCOOH). OH• species was chosen as the most likely candidate for the role of the oxidant for rCO2. Preliminary calculations for the expected reactions were carried out, and the optimal PES is revealed.

scholarly journals Role of Insulin in Health and Disease: An Update

2021 ◽  
Vol 22 (12) ◽  
pp. 6403
Author(s):  
Md Saidur Rahman ◽  
Khandkar Shaharina Hossain ◽  
Sharnali Das ◽  
Sushmita Kundu ◽  
Elikanah Olusayo Adegoke ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Basic Research ◽  
Future Research ◽  
Protective Effects ◽  
Glucose Levels ◽  
Physiological Processes ◽  
Blood Glucose Levels ◽  
Wide Range ◽  
Health And Disease

Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.

scholarly journals A modular tool to query and inducibly disrupt biomolecular condensates

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carmen N. Hernández-Candia ◽  
Sarah Pearce ◽  
Chandra L. Tucker
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cellular Function ◽  
Biological Role ◽  
Cellular Biology ◽  
Condensate Formation ◽  
Health And Disease ◽  
Lateral Sclerosis

AbstractDynamic membraneless compartments formed by protein condensates have multifunctional roles in cellular biology. Tools that inducibly trigger condensate formation have been useful for exploring their cellular function, however, there are few tools that provide inducible control over condensate disruption. To address this need we developed DisCo (Disassembly of Condensates), which relies on the use of chemical dimerizers to inducibly recruit a ligand to the condensate-forming protein, triggering condensate dissociation. We demonstrate use of DisCo to disrupt condensates of FUS, associated with amyotrophic lateral sclerosis, and to prevent formation of polyglutamine-containing huntingtin condensates, associated with Huntington’s disease. In addition, we combined DisCo with a tool to induce condensates with light, CRY2olig, achieving bidirectional control of condensate formation and disassembly using orthogonal inputs of light and rapamycin. Our results demonstrate a method to manipulate condensate states that will have broad utility, enabling better understanding of the biological role of condensates in health and disease.

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