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 Protective Effect of Qiliqiangxin Capsule on Energy Metabolism and Myocardial Mitochondria in Pressure Overload Heart Failure Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Junfang Zhang ◽  
Cong Wei ◽  
Hongtao Wang ◽  
Siwen Tang ◽  
Zhenhua Jia ◽  
...  
Keyword(s):  
Heart Failure ◽  
Energy Metabolism ◽  
Mitochondrial Function ◽  
Pressure Overload ◽  
Metabolic Intermediate ◽  
Substrate Metabolism ◽  
Myocardial Mitochondria ◽  
Tcm Theory

Qiliqiangxin capsule (QL) was developed under the guidance of TCM theory of collateral disease and had been shown to be effective and safe for the treatment of heart failure. The present study explored the role of and mechanism by which the herbal compounds QL act on energy metabolism,in vivo, in pressure overload heart failure. SD rats received ascending aorta constriction (TAC) to establish a model of myocardial hypertrophy. The animals were treated orally for a period of six weeks. QL significantly inhibited cardiac hypertrophy due to ascending aortic constriction and improved hemodynamics. This effect was linked to the expression levels of the signaling factors in connection with upregulated energy and the regulation of glucose and lipid substrate metabolism and with a decrease in metabolic intermediate products and the protection of mitochondrial function. It is concluded that QL may regulate the glycolipid substrate metabolism by activating AMPK/PGC-1αaxis and reduce the accumulation of free fatty acids and lactic acid, to protect cardiac myocytes and mitochondrial function.

Abstract 16870: Dissociation of Mitochondrial HK-II Triggers Mitochondria Specific Autophagy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Shigeki Miyamoto ◽  
David J Roberts ◽  
Valerie P Tan-Sah
Keyword(s):  
Energy Production ◽  
Ventricular Myocytes ◽  
Neonatal Rat ◽  
Mouse Heart ◽  
Hexokinase Ii ◽  
Survival Pathway ◽  
Mitochondrial Membrane Depolarization ◽  
Neonatal Rat Ventricular Myocytes

Introduction: There is emerging evidence that the metabolic pathway interplays with the survival pathway to preserve cellular homeostasis. Hexokinases (HKs) catalyze the first step of glucose metabolism and hexokinase-II (HK-II) is the predominant isoform in the heart. Our recent study revealed that HK-II positively regulates general autophagy in the absence of glucose. Mitochondrial HK-II (mitoHK-II) is regulated by Akt and provides cardioprotection while it is decreased in the ischemic heart. Hypothesis: We tested the hypothesis that mitoHK-II dissociation triggers mitochondria specific autophagy (mitophagy). Results: As previously reported, mitoHK-II levels were decreased by ~40% in the perfused mouse heart subjected to global ischemia and in neonatal rat ventricular myocytes (NRVMs) subjected to simulated ischemia. To assess the role of mitoHK-II dissociation, mitoHK-II dissociating peptide (15NG) was expressed in NRVMs. MitoHK-II was decreased by 40% in NRVMs expressing 15NG which was accompanied with Parkin translocation to mitochondria and ubiquitination of mitochondrial proteins. This response was attenuated by Parkin knockdown and reversed by the recovery of mitoHK-II by co-expression of HK-II but not by that of mitochondria binding deficient mutant. 15NG expression did not induce mitochondrial membrane depolarization nor PINK1 stabilization at mitochondria, suggesting that the effects of mitoHK-II dissociation is not dependent on the previously established mitochondria depolarization/PINK1 pathway. This was confirmed by the experiments using PINK1 siRNA. Modest dissociation of mitoHK-II (by 20%) did not induce mitophagic responses but remarkably enhanced FCCP induced mitophagy, indicating that these two pathways are synergetic. We will be analyzing 15NG transgenic mice generated in our lab to determine the mitophagic role of mitoHK-II dissociation in vivo. Conclusions: These results suggest that mitoHK-II dissociation can regulate Parkin dependent mitophagy, in conjunction with depolarization dependent mechanisms and that HK-II could confer cardioprotection by switching the cell from an energy production to an energy conservation mode under ischemia.

OZONE OXIDIZES OLEIC FATTY ACID WITH THE HIGHEST RATE CONSTANT AND DOES NOT OXIDIZE PALMITIC ACID. DIFFERENT PHYSICOCHEMICAL PARAMETERS OF SUBSTRATES AND THEIR ROLE IN PHYLOGENESIS

2019 ◽  
Vol 64 (3) ◽  
pp. 132-139
Author(s):  
Vladimir Nikolaevich Titov ◽  
N. N. Sazhina ◽  
N. M. Evteeva
Keyword(s):  
Physicochemical Parameters ◽  
Energy Production ◽  
Production Efficiency ◽  
Biological Function ◽  
Homo Sapiens ◽  
Mitochondrial Matrix ◽  
Oxidation Parameters ◽  
Nonalcoholic Liver Disease ◽  
Biological Organisms

Physicochemical differences between О3 oxidation parameters for palmitic and oleic fatty acids (FA) during phylogenesis (evolution) are fundamental for а) production of palmitoleic monounsaturated fatty (MFA), b) formation of carnitine palmitoyltransferase as a FA transporter to mitochondria, and c) in vivo production of oleic MFA under humoral regulatory effect of insulin. In the strive for the best kinetic parameters of biological organisms without a possibility of modifying physicochemical and biochemical reactions in the mitochondrial matrix, the mitochondria can be provided with a substrate that increases energy production efficiency and the amount of ATP. Physicochemical parameters of oleic MFA has become the standard of an oxidation substrate for in vivo energy production; this MFA was synthesized in organisms for millions of years. Environmental influences are the second factor which determines kinetic perfection of biological organisms during phylogenesis. Are these influences always beneficial? Mostly, they are not. However, they largely stimulate adaptive functions of the organism, including the biological function of locomotion, cognitive function and the function of positioning in the environment. Biological, energy and kinetic perfection formed in vivo can be easily destroyed if phylogenetically herbivorous Homo sapiens abuses the diet of carnivorous animals (meat) which was not consumed by him and his ancestors during phylogenesis. This abuse is the major cause of metabolic pandemias in human population. They are: insulin resistance, atherosclerosis and atheromatosis, obesity and nonalcoholic liver disease. The most effective measures preventing metabolic pandemias, cardiac heart disease and myocardial infarction are extremely simple. People should remain herbivorous.

scholarly journals A possible role of osteocalcin in the regulation of insulin secretion: human in vivo evidence?

2008 ◽  
Vol 199 (2) ◽  
pp. 151-153 ◽  
Author(s):  
Eva Kassi ◽  
Athanasios G Papavassiliou
Keyword(s):  
Insulin Secretion ◽  
Energy Metabolism ◽  
Glucose Metabolism ◽  
Gain Loss

Recent studies have indicated a novel function for skeleton unraveling its importance in the control of energy metabolism. In the present commentary, we speculate on the meaning for bone to act as a ‘rheostat’ modulating glucose metabolism, and how the primitive way of communication between bone and energy metabolism through switch on/off genes (like Ptprv) evolved to a more complicated ‘talking’ via gain/loss of hormones activity (like osteocalcin) by carboxylation/decarboxylation process.

Role of calcium in metabolic signaling between cardiac sarcoplasmic reticulum and mitochondria in vitro

2003 ◽  
Vol 284 (2) ◽  
pp. C285-C293 ◽  
Author(s):  
Robert S. Balaban ◽  
Salil Bose ◽  
Stephanie A. French ◽  
Paul R. Territo
Keyword(s):  
Energy Metabolism ◽  
Sarcoplasmic Reticulum ◽  
Atp Synthesis ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Atp Production ◽  
Wide Range ◽  
Reconstituted System

The role of Ca2+ as a cytosolic signaling molecule between porcine cardiac sarcoplasmic reticulum (SR) ATPase and mitochondrial ATP production was evaluated in vitro. The Ca2+ sensitivity of these processes was determined individually and in a reconstituted system with SR and mitochondria in a 0.5:1 protein-to-cytochrome aa 3 ratio. The half-maximal concentration ( K 1/2) of SR ATPase was 335 nM Ca2+. The ATP synthesis dependence was similar with a K 1/2 of 243 nM for dehydrogenases and 114 nM for overall ATP production. In the reconstituted system, Ca2+ increased thapsigargin-sensitive ATP production (maximum ∼5-fold) with minimal changes in mitochondrial reduced nicotinamide adenine dinucleotide (NADH). NADH concentration remained stable despite graded increases in NADH turnover induced over a wide range of Ca2+ concentrations (0 to ∼500 nM). These data are consistent with a balanced activation of SR ATPase and mitochondrial ATP synthesis by Ca2+ that contributes to a homeostasis of energy metabolism metabolites. It is suggested that this balanced activation by cytosolic Ca2+ is partially responsible for the minimal alteration in energy metabolism intermediates that occurs with changes in cardiac workload in vivo.

scholarly journals Sirtuin 3 deficiency does not impede digit regeneration in mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Emily Busse ◽  
Jennifer Simkin ◽  
Luis Marrero ◽  
Kennon Stewart ◽  
Regina Brunauer ◽  
...  
Keyword(s):  
Energy Production ◽  
Sirtuin 3 ◽  
Regenerative Capacity ◽  
Soft Tissue Regeneration ◽  
Bone Injury ◽  
Periosteal Cells ◽  
Deficient Mice

Abstract The mitochondrial deacetylase sirtuin 3 (SIRT3) is thought to be one of the main contributors to metabolic flexibility–promoting mitochondrial energy production and maintaining homeostasis. In bone, metabolic profiles are tightly regulated and the loss of SIRT3 has deleterious effects on bone volume in vivo and on osteoblast differentiation in vitro. Despite the prominent role of this protein in bone stem cell proliferation, metabolic activity, and differentiation, the importance of SIRT3 for regeneration after bone injury has never been reported. We show here, using the mouse digit amputation model, that SIRT3 deficiency has no impact on the regenerative capacity and architecture of bone and soft tissue. Regeneration occurs in SIRT3 deficient mice in spite of the reduced oxidative metabolic profile of the periosteal cells. These data suggest that bone regeneration, in contrast to homeostatic bone turnover, is not reliant upon active SIRT3, and our results highlight the need to examine known roles of SIRT3 in the context of injury.

scholarly journals Expression of the maize MnSod (Sod3) gene in MnSOD-deficient yeast rescues the mutant yeast under oxidative stress.

Genetics ◽  
1992 ◽  
Vol 131 (4) ◽  
pp. 803-809 ◽  
Author(s):  
D Zhu ◽  
J G Scandalios
Keyword(s):  
Oxidative Stress ◽  
Yeast Strain ◽  
Functional Role ◽  
Transit Peptide ◽  
Yeast Cells ◽  
Mitochondrial Matrix ◽  
Higher Plant ◽  
Initial Portion

Abstract Superoxide dismutases (SOD) are ubiquitous in aerobic organisms and are believed to play a significant role in protecting cells against the toxic, often lethal, effect of oxygen free radicals. However, direct evidence that SOD does in fact participate in such a protective role is scant. The MnSOD-deficient yeast strain (Sod2d) offered an opportunity to test the functional role of one of several SOD isozymes from the higher plant maize in hopes of establishing a functional bioassay for other SODs. Herein, we present evidence that MnSOD functions to protect cells from oxidative stress and that this function is conserved between species. The maize Sod3 gene was introduced into the yeast strain Sod2d where it was properly expressed and its product processed into the yeast mitochondrial matrix and assembled into the functional homotetramer. Most significantly, expression of the maize Sod3 transgene in yeast rendered the transformed yeast cells resistant to paraquat-induced oxidative stress by complementing the MnSOD deficiency. Furthermore, analyses with various deletion mutants of the maize SOD-3 transit peptide in the MnSOD-deficient yeast strain indicate that the initial portion (about 8 amino acids) of the maize transit peptide is required to direct the protein into the yeast mitochondrial matrix in vivo to function properly. These findings indicate that the functional role of maize MnSOD is conserved and dependent on its proper subcellular location in the mitochondria of a heterologous system.

scholarly journals Alternative Methods for Mitochondrial Transplantation: Efficiency of Unpackaged and Lipid-Packaged Preparations

2017 ◽  
Author(s):  
DL McPhie ◽  
LW Sargent ◽  
SM Babb ◽  
D Ben-Shachar ◽  
AM Cataldo ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Animal Models ◽  
Membrane Lipids ◽  
Recipient Cell ◽  
Cell Uptake ◽  
Alternative Methods ◽  
Mitochondrial Matrix ◽  
Injection Techniques ◽  
Transplant Experiments

AbstractMitochondrial transplantation is currently being explored as a means to repair and restore proper organelle function in a variety of inherited and acquired disorders of energy metabolism. The optimal preparation and application of donor mitochondria is unknown, but most studies in vivo have used injection techniques or, for tissue studies, unpackaged mitochondria (organelles isolated and suspended in buffer) in transplant experiments. Packaging in lipid rafts can increase recipient cell uptake of some compounds and objects. We present the first data comparing recipient cell uptake of unpackaged mitochondria to recipient cell uptake of mitochondria packaged in cell membrane lipids. Mitochondria and membranes were prepared from autologous cells and applied to cells (fibroblasts) in culture. Both unpackaged and lipid-packaged mitochondria were taken into recipient cells and the donor mitochondria showed evidence, in each case, of retained functionality and the ability to merge with the recipient mitochondrial matrix. However, lipid packaging appeared to enhance the uptake of functional mitochondria. Current studies of mitochondrial transplantation in animal models might fruitfully explore the utility and efficacy of lipid-packaged mitochondria in transplant experiments.

scholarly journals GTP in the mitochondrial matrix plays a crucial role in organellar iron homoeostasis1

2006 ◽  
Vol 400 (1) ◽  
pp. 163-168 ◽  
Author(s):  
Donna M. Gordon ◽  
Elise R. Lyver ◽  
Emmanuel Lesuisse ◽  
Andrew Dancis ◽  
Debkumar Pain
Keyword(s):  
Nucleoside Diphosphate Kinase ◽  
Mitochondrial Matrix ◽  
Yeast Saccharomyces Cerevisiae ◽  
Iron Sulfur Clusters ◽  
Cellular Iron ◽  
Iron Sulfur ◽  
The Matrix ◽  
Cellular Iron Uptake

Mitochondria are the major site of cellular iron utilization for the synthesis of essential cofactors such as iron–sulfur clusters and haem. In the present study, we provide evidence that GTP in the mitochondrial matrix is involved in organellar iron homoeostasis. A mutant of yeast Saccharomyces cerevisiae lacking the mitochondrial GTP/GDP carrier protein (Ggc1p) exhibits decreased levels of matrix GTP and increased levels of matrix GDP [Vozza, Blanco, Palmieri and Palmieri (2004) J. Biol. Chem. 279, 20850–20857]. This mutant (previously called yhm1) also manifests high cellular iron uptake and tremendous iron accumulation within mitochondria [Lesuisse, Lyver, Knight and Dancis (2004) Biochem. J. 378, 599–607]. The reason for these two very different phenotypic defects of the same yeast mutant has so far remained elusive. We show that in vivo targeting of a human nucleoside diphosphate kinase (Nm23-H4), which converts ATP into GTP, to the matrix of ggc1 mutants restores normal iron regulation. Thus the role of Ggc1p in iron metabolism is mediated by effects on GTP/GDP levels in the mitochondrial matrix.

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