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Special Issue "Molecular System Bioenergetics 2011"

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry, Molecular and Cellular Biology".

Deadline for manuscript submissions: closed (11 October 2011)

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Special Issue Editors

Guest Editor Dr. Valdur Saks Laboratory of Bioenergetics, INSERM U884, Joseph Fourier University, Grenoble, France E-Mail Phone: +33476635627 Fax: +33 4 7651 4218 Interests: bioenergetics; systems biology; biophysics; enzymology; cell physiology
Guest Editor Dr. Rita Guzun Laboratory of Bioenergetics, INSERM U884, Joseph Fourier University, Grenoble, France E-Mail

Special Issue Information

Dear Colleagues,

This Special Issue is a sequel of the previous IJMS issues “Molecular System Bioenergetics” and “Quantitative Modeling in Molecular System Bioenergetics”.

The purpose of the present Issue is to describe and discuss the advanced research in the field of the Molecular System Bioenergetics including experimental and computational studies. Special interest has been focused on the dynamic organization of metabolic networks, their functioning in the tight interaction with intracellular elements (mitochondria-cytoskeleton-myofibrils- membranes) and the role of mitochondrial dynamics (fusion/fission) for cellular metabolism. Other highly important subject of discussion is molecular mechanisms of the energy metabolism regulation including experimental studies such as Metabolic Control Analyses, metabolome’s studies and mathematical modeling. Papers on application of this integrative approach for the analysis of the energy metabolism of biological systems at different degree of their complexity (cells, tissue, organs) in health and pathology (including oxidative stress, apoptosis, etc) will be welcome. This Systems Biology approach will be increasingly important for studies of both biological and medical problems.

Dr. Rita Guzun
Dr. Valdur Saks
Guest Editors

Keywords

energy metabolism
regulation
mitochondria
respiration
cytoskeleton
fusion/fission
modeling
Systems Biology

Published Papers (5 papers)

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Editorial

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Open AccessEditorial Molecular System Bioenergics of the Heart: Experimental Studies of Metabolic Compartmentation and Energy Fluxes versus Computer Modeling

by Mayis Aliev, Rita Guzun, Minna Karu-Varikmaa, Tuuli Kaambre, Theo Wallimann and Valdur Saks

Int. J. Mol. Sci. 2011, 12(12), 9296-9331; https://doi.org/10.3390/ijms12129296

Received: 10 November 2011 / Revised: 30 November 2011 / Accepted: 30 November 2011 / Published: 13 December 2011

Cited by 15 | PDF Full-text (801 KB) | HTML Full-text | XML Full-text

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In this review we analyze the recent important and remarkable advancements in studies of compartmentation of adenine nucleotides in muscle cells due to their binding to macromolecular complexes and cellular structures, which results in non-equilibrium steady state of the creatine kinase reaction. We discuss the problems of measuring the energy fluxes between different cellular compartments and their simulation by using different computer models. Energy flux determinations by ¹⁸O transfer method have shown that in heart about 80% of energy is carried out of mitochondrial intermembrane space into cytoplasm by phosphocreatine fluxes generated by mitochondrial creatine kinase from adenosine triphosphate (ATP), produced by ATP Synthasome. We have applied the mathematical model of compartmentalized energy transfer for analysis of experimental data on the dependence of oxygen consumption rate on heart workload in isolated working heart reported by Williamson et al. The analysis of these data show that even at the maximal workloads and respiration rates, equal to 174 µmol O₂ per min per g dry weight, phosphocreatine flux, and not ATP, carries about 80–85% percent of energy needed out of mitochondria into the cytosol. We analyze also the reasons of failures of several computer models published in the literature to correctly describe the experimental data. Full article

(This article belongs to the Special Issue Molecular System Bioenergetics 2011)

Research

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Open AccessArticle Glucose-Modulated Mitochondria Adaptation in Tumor Cells: A Focus on ATP Synthase and Inhibitor Factor 1

by Rossana Domenis, Elena Bisetto, Davide Rossi, Marina Comelli and Irene Mavelli

Int. J. Mol. Sci. 2012, 13(2), 1933-1950; https://doi.org/10.3390/ijms13021933

Received: 31 October 2011 / Revised: 6 January 2012 / Accepted: 30 January 2012 / Published: 10 February 2012

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Warburg’s hypothesis has been challenged by a number of studies showing that oxidative phosphorylation is repressed in some tumors, rather than being inactive per se. Thus, treatments able to shift energy metabolism by activating mitochondrial pathways have been suggested as an intriguing basis for the optimization of antitumor strategies. In this study, HepG2 hepatocarcinoma cells were cultivated with different metabolic substrates under conditions mimicking “positive” (activation/biogenesis) or “negative” (silencing) mitochondrial adaptation. In addition to the expected up-regulation of mitochondrial biogenesis, glucose deprivation caused an increase in phosphorylating respiration and a rise in the expression levels of the ATP synthase β subunit and Inhibitor Factor 1 (IF1). Hyperglycemia, on the other hand, led to a markedly decreased level of the transcriptional coactivator PGC-α suggesting down-regulation of mitochondrial biogenesis, although no change in mitochondrial mass and no impairment of phosphorylating respiration were observed. Moreover, a reduction in mitochondrial networking and in ATP synthase dimer stability was produced. No effect on β-ATP synthase expression was elicited. Notably, hyperglycemia caused an increase in IF1 expression levels, but it did not alter the amount of IF1 associated with ATP synthase. These results point to a new role of IF1 in relation to high glucose utilization by tumor cells, in addition to its well known effect upon mitochondrial ATP synthase regulation. Full article

(This article belongs to the Special Issue Molecular System Bioenergetics 2011)

Open AccessArticle A Mitochondrial Membrane Exopolyphosphatase Is Modulated by, and Plays a Role in, the Energy Metabolism of Hard Tick Rhipicephalus (Boophilus) microplus Embryos

by Eldo Campos, Arnoldo R. Façanha, Evenilton P. Costa, Amanda Fraga, Jorge Moraes, Itabajara Da Silva Vaz Jr., Aoi Masuda and Carlos Logullo

Int. J. Mol. Sci. 2011, 12(6), 3525-3535; https://doi.org/10.3390/ijms12063525

Received: 22 April 2011 / Revised: 14 May 2011 / Accepted: 19 May 2011 / Published: 3 June 2011

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The physiological roles of polyphosphates (polyP) recently found in arthropod mitochondria remain obscure. Here, the relationship between the mitochondrial membrane exopolyphosphatase (PPX) and the energy metabolism of hard tick Rhipicephalus microplus embryos are investigated. Mitochondrial respiration was activated by adenosine diphosphate using polyP as the only source of inorganic phosphate (P_i) and this activation was much greater using polyP₃ than polyP₁₅. After mitochondrial subfractionation, most of the PPX activity was recovered in the membrane fraction and its kinetic analysis revealed that the affinity for polyP₃ was 10 times stronger than that for polyP₁₅. Membrane PPX activity was also increased in the presence of the respiratory substrate pyruvic acid and after addition of the protonophore carbonyl cyanide-p-trifluoromethoxyphenylhydrazone. Furthermore, these stimulatory effects disappeared upon addition of the cytochrome oxidase inhibitor potassium cyanide and the activity was completely inhibited by 20 µg/mL heparin. The activity was either increased or decreased by 50% upon addition of dithiothreitol or hydrogen peroxide, respectively, suggesting redox regulation. These results indicate a PPX activity that is regulated during mitochondrial respiration and that plays a role in adenosine-5’-triphosphate synthesis in hard tick embryos. Full article

(This article belongs to the Special Issue Molecular System Bioenergetics 2011)

Review

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Open AccessReview Yeast Mitochondrial Interactosome Model: Metabolon Membrane Proteins Complex Involved in the Channeling of ADP/ATP

by Benjamin Clémençon

Int. J. Mol. Sci. 2012, 13(2), 1858-1885; https://doi.org/10.3390/ijms13021858

Received: 11 November 2011 / Revised: 20 January 2012 / Accepted: 31 January 2012 / Published: 10 February 2012

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The existence of a mitochondrial interactosome (MI) has been currently well established in mammalian cells but the exact composition of this super-complex is not precisely known, and its organization seems to be different from that in yeast. One major difference is the absence of mitochondrial creatine kinase (MtCK) in yeast, unlike that described in the organization model of MI, especially in cardiac, skeletal muscle and brain cells. The aim of this review is to provide a detailed description of different partner proteins involved in the synergistic ADP/ATP transport across the mitochondrial membranes in the yeast Saccharomyces cerevisiae and to propose a new mitochondrial interactosome model. The ADP/ATP (Aacp) and inorganic phosphate (PiC) carriers as well as the VDAC (or mitochondrial porin) catalyze the import and export of ADP, ATP and Pi across the mitochondrial membranes. Aacp and PiC, which appear to be associated with the ATP synthase, consist of two nanomotors (F₀, F₁) under specific conditions and form ATP synthasome. Identification and characterization of such a complex were described for the first time by Pedersen and co-workers in 2003. Full article

(This article belongs to the Special Issue Molecular System Bioenergetics 2011)

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Open AccessReview Hormonal Influence on Coenzyme Q₁₀ Levels in Blood Plasma

by Antonio Mancini, Roberto Festa, Sebastiano Raimondo, Alfredo Pontecorvi and Gian Paolo Littarru

Int. J. Mol. Sci. 2011, 12(12), 9216-9225; https://doi.org/10.3390/ijms12129216

Received: 1 November 2011 / Revised: 19 November 2011 / Accepted: 29 November 2011 / Published: 9 December 2011

Cited by 12 | PDF Full-text (364 KB) | HTML Full-text | XML Full-text

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Coenzyme Q₁₀ (CoQ₁₀), also known as ubiquinone for its presence in all body cells, is an essential part of the cell energy-producing system. However, it is also a powerful lipophilic antioxidant protecting lipoproteins and cell membranes. Due to these two actions, CoQ₁₀ is commonly used in clinical practice in chronic heart failure, male infertility, and neurodegenerative disease. However, it is also taken as an anti-aging substance by healthy people aiming for long-term neuroprotection and by sportsmen to improve endurance. Many hormones are known to be involved in body energy regulation, in terms of production, consumption and dissipation, and their influence on CoQ₁₀ body content or blood values may represent an important pathophysiological mechanism. We summarize the main findings of the literature about the link between hormonal systems and circulating CoQ₁₀ levels. In particular the role of thyroid hormones, directly involved in the regulation of energy homeostasis, is discussed. There is also a link with gonadal and adrenal hormones, partially due to the common biosynthetic pathway with CoQ₁₀, but also to the increased oxidative stress found in hypogonadism and hypoadrenalism. Full article

(This article belongs to the Special Issue Molecular System Bioenergetics 2011)

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