Mitochondrial energetic metabolism: A simplified model of TCA cycle with ATP production (original) (raw)
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Mitochondrial energetic metabolism-some general principles
IUBMB life, 2013
SummaryIn 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 respiratory complexes, ATP synthase, and ATP/adenosine diphosphate (ADP) carrier are now quite well known, the coupling between ATP synthesis and cell redox state remains a controversial issue. In this review, we will present some of the processes that allow a modular coupling between ATP synthesis and redox state. Furthermore, we will present some theoretical approaches of this highly integrated system. © 2013 IUBMB Life, 65(3):171–179, 2013
A simplified model for mitochondrial ATP production
Journal of Theoretical Biology, 2006
Most of the adenosine triphosphate (ATP) synthesized during glucose metabolism is produced in the mitochondria through oxidative phosphorylation. This is a complex reaction powered by the proton gradient across the mitochondrial inner membrane, which is generated by mitochondrial respiration. A detailed model of this reaction, which includes dynamic equations for the key mitochondrial variables, was developed earlier by Magnus and Keizer. However, this model is extraordinarily complicated. We develop a simpler model that captures the behavior of the original model but is easier to use and to understand. We then use it to investigate the mitochondrial responses to glycolytic and calcium input. We use the model to explain experimental observations of the opposite effects of raising cytosolic Ca 2þ in low and high glucose, and to predict the effects of a mutation in the mitochondrial enzyme nicotinamide nucleotide transhydrogenase (Nnt) in pancreatic b-cells.
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Mathematical Biosciences, 2021
We present a computational framework for analyzing and simulating mitochondrial ATP synthesis using basic thermodynamic and kinetic principles. The framework invokes detailed descriptions of the thermodynamic driving forces associated with the processes of the electron transport chain, mitochondrial ATP synthetase, and phosphate and adenine nucleotide transporters. Assembling models of these discrete processes into an integrated model of mitochondrial ATP synthesis, we illustrate how to analyze and simulate in vitro respirometry experiments and how models identified from in vitro experimental data effectively explain cardiac respiratory control in vivo. Computer codes for these analyses are embedded as Python scripts in a Jupyter Book to facilitate easy adoption and modification of the concepts developed here. This accessible framework may also prove useful in supporting educational applications. All source codes are available on at https://beards-lab.github.io/QAMAS\_book/.
Mitochondrial respiratory chain adjustment to cellular energy demand
Journal of Biological …, 2001
Because adaptation to physiological changes in cellular energy demand is a crucial imperative for life, mitochondrial oxidative phosphorylation is tightly controlled by ATP consumption. Nevertheless, the mechanisms permitting such large variations in ATP synthesis capacity, as well as the consequence on the overall efficiency of oxidative phosphorylation, are not known. By investigating several physiological models in vivo in rats (hyper-and hypothyroidism, polyunsaturated fatty acid deficiency, and chronic ethanol intoxication) we found that the increase in hepatocyte respiration (from 9.8 to 22.7 nmol of O 2 /min/mg dry cells) was tightly correlated with total mitochondrial cytochrome content, expressed both per mg dry cells or per mg mitochondrial protein. Moreover, this increase in total cytochrome content was accompanied by an increase in the respective proportion of cytochrome oxidase; while total cytochrome content increased 2-fold (from 0.341 ؎ 0.021 to 0.821 ؎ 0.024 nmol/mg protein), cytochrome oxidase increased 10-fold (from 0.020 ؎ 0.002 to 0.224 ؎ 0.006 nmol/mg protein). This modification was associated with a decrease in the overall efficiency of the respiratory chain. Since cytochrome oxidase is well recognized for slippage between redox reactions and proton pumping, we suggest that this dramatic increase in cytochrome oxidase is responsible for the decrease in the overall efficiency of respiratory chain and, in turn, of ATP synthesis yield, linked to the adaptive increase in oxidative phosphorylation capacity. The abbreviations used are: ATP/O, adenosine triphosphate synthesis (nmol/min/mg protein)/oxygen consumption rate (nanoatom/min/ mg); PUFA, polyunsaturated fatty acid; ⌬⌿, electrical potential difference across the mitochondrial inner membrane; TPMP ϩ , trimephenylmethylphosphonium ion; ⌬EЈh, Gibbs free-energy difference in oxidation reaction (redox potential); DNP, 2,4-dinitrophenol; J O 2 , oxygen consumption rate; ANC, adenine nucleotide carrier.
Mitochondrial respiratory states and rates: building blocks of mitochondrial physiology
Biochimica et Biophysica Acta (BBA) - Bioenergetics, 2018
This manuscript on 'Mitochondrial respiratory states and rates' is a position statement in the frame of COST Action CA15203 MitoEAGLE. The list of co-authors evolved beyond phase 1 (phase 1 versions 1-44) in the bottom-up spirit of COST. This is an open invitation to scientists and students to join as co-authors, to provide a balanced view on mitochondrial respiratory control, a fundamental introductory presentation of the concept of the protonmotive force, and a consensus statement on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Phase 2: MitoEAGLE preprint 'The protonmotive force and respiratory control' (Versions 01-21): We continue to invite comments and suggestions, particularly if you are an early career investigator adding an open future-oriented perspective, or an established scientist providing a balanced historical basis. Your critical input into the quality of the manuscript will be most welcome, improving our aims to be educational, general, consensusoriented, and practically helpful for students working in mitochondrial respiratory physiology.
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Consortium communication Mitochondrial physiology Gnaiger Erich et al (MitoEAGLE Task Group)* Living Communication: extended resource of Mitochondrial respiratory states and rates.
Journal of Biological Chemistry, 2007
A computational model of mitochondrial metabolism and electrophysiology is introduced and applied to analysis of data from isolated cardiac mitochondria and data on phosphate metabolites in striated muscle in vivo. This model is constructed based on detailed kinetics and thermodynamically balanced reaction mechanisms and a strict accounting of rapidly equilibrating biochemical species. Since building such a model requires introducing a large number of adjustable kinetic parameters, a correspondingly large amount of independent data from isolated mitochondria respiring on different substrates and subject to a variety of protocols is used to parameterize the model and ensure that it is challenged by a wide range of data corresponding to diverse conditions. The developed model is further validated by both in vitro data on isolated cardiac mitochondria and in vivo experimental measurements on human skeletal muscle. The validated model is used to predict the roles of NAD and ADP in regulating the tricarboxylic acid cycle dehydrogenase fluxes, demonstrating that NAD is the more important regulator. Further model predictions reveal that a decrease of cytosolic pH value results in decreases in mitochondrial membrane potential and a corresponding drop in the ability of the mitochondria to synthesize ATP at the hydrolysis potential required for cellular function.
Physiological implications of linear kinetics of mitochondrial respiration in vitro
AJP: Cell Physiology, 2008
TO THE EDITOR: Glancy et al. (4) measure the rate of oxygen consumption (J o ) by mitochondria incubated with an ATPconsuming system in the presence of creatine kinase (CK), and they show that this in vitro model of aerobically exercising skeletal muscle conforms to Meyer's electrical analog of muscle oxidative phosphorylation in vivo (23). I want to suggest that the interpretation of these experiments is enhanced by distinguishing the specific features of this model from general properties of feedback control (see 1-8 below), and making explicit its relationship (see ) to alternative models .