Jean-Pierre Mazat

Jean-Pierre Mazat
University of Bordeaux · Biochemistry

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176
Publications
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6,369
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Publications

Publications (176)
Article
Full-text available
The m.8993T>G mutation of the mitochondrial MT-ATP6 gene is associated with NARP syndrome (neuropathy, ataxia and retinitis pigmentosa). The equivalent point mutation introduced in yeast Saccharomyces cerevisiae mitochondrial DNA considerably reduced the activity of ATP synthase and of cytochrome-c-oxidase, preventing yeast growth on oxidative subs...
Preprint
Full-text available
The m.8993T>G mutation of the mitochondrial MT-ATP6 gene is associated with NARP syndrome (Neuropathy, Ataxia and Retinitis Pigmentosa). The equivalent point mutation introduced in yeast Saccharomyces cerevisiae mitochondrial DNA considerably reduced the activity of ATP synthase and of cytochrome-C-oxidase preventing yeast growth on oxidative subst...
Chapter
Mitochondria are double-membrane-enclosed organelles that ensure a number of central functions in the vast majority of eukaryotic cells. These include, among others, key steps in lipid and amino acid metabolism, biosynthesis of iron–sulfur clusters, heme, and further prosthetic groups, regulation of programmed cell death, and most prominently the f...
Article
In living cells, growth is the result of coupling between substrate catabolism and multiple metabolic processes that take place during net biomass formation and maintenance processes. During growth, both ATP/ADP and NADH/NAD⁺ molecules play a key role. Cell energy metabolism hence refers to metabolic pathways involved in ATP synthesis linked to NAD...
Article
Full-text available
ROS (superoxide and oxygen peroxide in this paper) play a dual role as signalling molecules and strong oxidizing agents leading to oxidative stress. Their production mainly occurs in mitochondria although they may have other locations (such as NADPH oxidase in particular cell types). Mitochondrial ROS production depends in an interweaving way upon...
Article
Full-text available
Genome-scale models of metabolism (GEM) are used to study how metabolism varies in different physiological conditions. However, the great number of reactions involved in GEM makes it difficult to understand these variations. In order to have a more understandable tool, we developed a reduced metabolic model of central carbon and nitrogen metabolism...
Article
Protein synthesis and degradation are essential processes that regulate cell status. Because labeling in bulky organs, such as fruits, is difficult, we developed a modeling approach to study protein turnover at the global scale in developing tomato (Solanum lycopersicum) fruit. Quantitative data were collected for transcripts and proteins during fr...
Article
Full-text available
The influence of pH on the activity of cytochrome c oxidase is investigated using the stochastic modelling based on Markov processes. The functioning of the K-channel is considered on four different schemes. A change of channel modes can be observed under high values of pH: the fraction of K-protons transferred through the membrane increases signif...
Preprint
Full-text available
Genome-scale models of metabolism (GEM) are used to study how metabolism varies in different physiological conditions. However, the great number of reactions involved in GEM makes it difficult to understand these variations. In order to have a more understandable tool, we developed a reduced metabolic model of central carbon and nitrogen metabolism...
Article
Full-text available
Evidence for the Crabtree effect was first reported by H. Crabtree in 1929 and is defined as the glucose-induced decrease of cellular respiratory flux. This effect was observed in tumor cells and was not detected in most non-tumor cells. A number of hypotheses on the mechanism underlying the Crabtree effect have been formulated. However, to this da...
Data
Video S1 Flux maps of water stress compared with control.
Data
Fig. S1 Fumarate concentration throughout tomato fruit development. Fig. S2 Fit of the accumulated metabolites and biomass compounds. Fig. S3 Importance of dissipating fluxes, AOX and UCP, on calculated fluxes. Fig. S4 Plant culture and fruit characterization. Fig. S5 Fruit composition throughout development. Fig. S6 Origin of CO2 released thr...
Data
Appendix S8. Fitting parameters of the accumulated metabolites and biomass components.
Article
The mitochondrial respiratory chain plays a crucial role in energy metabolism and its dysfunction is implicated in a wide range of human diseases. In order to understand the global expression of local mutations in the rate of oxygen consumption or in the production of ATP it is useful to have a mathematical model in which the changes in a given res...
Article
Full-text available
Modelling of metabolic networks is a powerful tool to analyse the behaviour of developing plant organs including fruits. Guided by current understanding on heterotrophic metabolism of plant cells, a medium-scale stoichiometric model, including the balance of cofactors and energy, was constructed in order to describe metabolic shifts that occur thro...
Article
Victor Henri's great contribution to the understanding of enzyme kinetics and mechanism is not always given the credit that it deserves. In addition, his earlier work in experimental psychology is totally unknown to biochemists, and his later work in spectroscopy and photobiology almost equally so. Applying great rigour to his analysis he succeeded...
Article
Full-text available
A kinetic model combining enzyme activity measurements and subcellular compartmentation was parameterized to fit the sucrose, hexose, and glucose-6-P contents of pericarp throughout tomato (Solanum lycopersicum) fruit development. The model was further validated using independent data obtained from domesticated and wild tomato species and on transg...
Article
Full-text available
To assess the influence of the environment on fruit metabolism, Tomato (Solanum lycopersicum) cv. Moneymaker plants were grown under contrasting conditions (optimal for commercial production, water limitation or shading) and locations. Samples were harvested at nine stages of development and 36 enzymes activities of central metabolism were measured...
Article
There are several theoretical approaches to metabolism. Some of them give a greater place to the structure of the metabolic network symbolized by its stoichiometry matrix. The constraints in a metabolic network are very strong so that a lot of information can be derived from the stoichiometry matrix without any knowledge of the kinetic parameters o...
Article
Full-text available
Methods and equations for analysing the kinetics of enzyme-catalysed reactions were developed at the beginning of the 20th century in two centres in particular, in Paris by Victor Henri, and in Berlin by Leonor Michaelis and Maud Menten. Henri made a detailed analysis of the work in this area that had preceded him, and arrived at a correct equation...
Article
Summary In nonphotosynthetic organisms, mitochondria are the power plant of the cell, emphasizing their great potentiality for adenosine triphosphate (ATP) synthesis from the redox span between nutrients and oxygen. Also of great importance is their role in the maintenance of the cell redox balance. Even though crystallographic structures of respir...
Article
The respiratory chain is located in the inner membrane of mitochondria and produces the major part of the ATP used by a cell. Cardiolipin (CL), a double charged phospholipid composing ~10-20% of the mitochondrial membrane, plays an important role in the function and supra-molecular organization of the respiratory chain complexes. We present an exte...
Article
Full-text available
The bc(1) complex or complex III is a central component of the aerobic respiratory chain in prokaryotic and eukaryotic organisms. It catalyses the oxidation of quinols and the reduction of cytochrome c, establishing a proton motive force used to synthesize ATP by the F(1)F(o) ATP synthase. In eukaryotes, the bc(1) complex is located in the inner mi...
Article
The modelling of OXPHOS (oxidative phosphorylation) in order to integrate all kinetic and thermodynamic aspects of chemiosmotic theory has a long history. We briefly review this history and show how new ways of modelling are required to integrate a local model of the individual respiratory complexes into a global model of OXPHOS and, beyond that, i...
Article
An enzyme's activity is the consequence of its structure. The stochastic approach we developed to study the functioning of the respiratory complexes is based upon their 3D structure and their physical and chemical properties. Consequently it should predict their kinetic properties. In this paper we compare the predictions of our stochastic model de...
Article
We use some examples to show that Metabolic Control Theory (MTC) not only allows the determination of the controlling steps of a metabolic network with the so-called control coefficients, but also leads to better understanding of the functioning of metabolic networks. The examples are taken partly from our own work on mitochondrial myopathies, part...
Article
Elementary flux mode analysis is a powerful tool for the theoretical study of metabolic networks. However, when the networks are complex, the determination of elementary flux modes leads to combinatorial explosion of their number which prevents from drawing simple conclusions from their analysis. To deal with this problem we have developed a method...
Article
Full-text available
Chronic hypoxia alters mitochondrial energy metabolism. In the heart, oxidative capacity of both ventricles is decreased after 3 weeks of chronic hypoxia. The aim of this study was to evaluate the reversal of these metabolic changes upon normoxia recovery. Rats were exposed to a hypobaric environment for 3 weeks and then subjected to a normoxic env...
Article
Using a stochastic simulation without any other hypotheses, we recently demonstrated the natural emergence of the modified Mitchell Q-cycle in the functioning of the bc(1) complex, with few short-circuits and a very low residence time of the reactive semiquinone species in the Q(o) site. However, this simple model fails to explain both the inhibiti...
Article
Full-text available
The bc1 complex is a central complex in the mitochondrial respiratory chain. It links the electrons transfer from ubiquinol (or coenzyme Q) to cytochrome c and proton translocation across the inner mitochondrial membrane. It is widely agreed that the "Q-cycle mechanism" proposed by Mitchell correctly describes the bc1 complex working. It is based o...
Article
Full-text available
The modelling of OXPHOS (oxidative phosphorylation) in order to integrate all kinetic and thermodynamic aspects of chemiosmotic theory has a long history. We briefly review this history and show how new ways of modelling are required to integrate a local model of the individual respiratory complexes into a global model of OXPHOS and, beyond that, i...
Article
A stochastic approach based on the Gillespie algorithm is particularly well adapted to describe the time course of the redox reactions that occur inside the respiratory chain complexes because they involve the motion of single electrons between the individual unique redox centres of a given complex. We use this approach to describe the molecular fu...
Article
Mitochondria play a central role in cellular energetic metabolism. The essential parts of this metabolism are the tricarboxylic acid (TCA) cycle, the respiratory chain and the adenosine triphosphate (ATP) synthesis machinery. Here a simplified model of these three metabolic components with a limited set of differential equations is presented. The e...
Article
Diversity of respiratory chain spectrophotometric assays may lead to difficult comparison of results between centers. The French network of mitochondrial diseases diagnostic centers undertook comparison of the results obtained with different protocols in the French diagnostic centers. The diversity of protocols was shown to have striking consequenc...
Article
Metabolic pathways describe chains of enzymatic reactions. Their modelling is a key point to understand living systems. An enzymatic reaction is an interaction between one or several metabolites (substrates) and an enzyme (simple protein or enzymatic complex build of several subunits). In our Mitochondria in Silico Project, MitoScop, we study the m...
Chapter
Full-text available
In smooth muscle cells (SMC), Ca2+ regulates several key functions like cell division, growth and cell death, as well as smooth muscle contractility. Mitochondria are intracellular compartments capable of Ca2+ uptake and release mainly via the mitochondrial uniporter and the mitochondrial Ca2+-Na+ exchanger, respectively. Thus mitochondria can cons...
Article
A stochastic approach based on Gillespie algorithm is particularly well adapted to describe the time course of the redox reactions that occur inside the respiratory chain complexes because they involve the motion of single electrons between individual unique redox centres of a given complex and not populations of electrons and redox centres as usua...
Article
We revisit an old Russian paper by V.V. Dynnik, R. Heinrich and E.E. Sel'kov (1980a,b) describing: "A mathematical model of carbohydrate energy metabolism. Interaction between glycolysis, the Krebs cycle and the H-transporting shuttles at varying ATPases load". We analyse the model mathematically and calculate the control coefficients as a function...
Article
Since twenty years, more and more crystallographic structures of enzymatic macromolecular complexes are available in international data banks. Movements of large protein structures are key components in ligand docking and enzymatic catalysis. Simulations of enzymatic reactions must take into account such structural movements. Our aim is to combine...
Article
The structural analysis of large metabolic networks exhibits a combinatorial explosion of elementary modes. A new method of classification has been developed [called aggregation around common motif (ACoM)], which groups elementary modes into classes with similar substructures. This method is applied to the tricarboxylic acid cycle and metabolite ca...
Article
Intracellular amyloid beta-peptide (A beta) accumulation is considered to be a key pathogenic factor in sporadic Alzheimer's disease (AD), but the mechanisms by which it triggers neuronal dysfunction remain unclear. We hypothesized that gradual mitochondrial dysfunction could play a central role in both initiation and progression of sporadic AD. Th...
Article
The present study was designed to characterize mitochondrial adaptation to chronic hypoxia (CH) in the rat heart. Mitochondrial energy metabolism was differentially examined in both left and right ventricles since CH selectively triggers pulmonary hypertension and right ventricular hypertrophy. Rats were exposed to a hypobaric environment for 2 or...
Article
Recent advances in cell biology have helped to create a picture of mitochondrial organization where the organelle exists as a single dynamic network (mt-network), either forming a reticulum or a fragmented collection of vesicles. Several observations have revealed that its tridimensional organization is variable in human living cells, both under no...
Article
To assess mitochondrial metabolism of bladder tissue induced by small-intestinal submucosa (SIS), by comparing the mitochondrial enzyme metabolism in this tissue with that in normal bladder tissue and thus evaluate intracellular normality. In all, 70 rats were grouped into healthy controls (10), surgical controls with a simple bladder incision (15)...
Article
Full-text available
Phosphatidylserine exposure in platelets is required for normal haemostasis and is also a hallmark of apoptosis. It results from activation of a phospholipid scramblase, which has been shown to be differently stimulated by Ca(2+)-influx and during apoptosis, thus suggesting that mitochondria may be involved in phosphatidylserine exposure in platele...
Article
Full-text available
Long-term preservation of muscle mitochondria for consequent functional analysis is an important and still unresolved challenge in the clinical study of metabolic diseases and in the basic research of mitochondrial physiology. We here present a method for cryopreservation of mitochondria in various muscle types including human biopsies. Mitochondri...
Article
Inside the eukaryotic cell, mitochondria are internal organelles of prokaryotic origin, responsible for energy supply in the cell. The control of the mitochondrial ATP production is a complex problem with different patterns according to different tissues and organs.
Article
The enzymatic activities of threonine pathway in Escherichia coli are sensitive to pollutants such as cadmium, copper and mercury, which, even at low concentration, can substantially decrease or even block the pathway at several steps. Our aim was to investigate the complex effects on a metabolic pathway of such general enzyme inhibitors with sever...
Article
Full-text available