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Wu 2007 J Biol Chem

From Bioblast
Publications in the MiPMap
Wu F, Yang F, Vinnakota KC, Beard DA (2007) Computer modeling of mitochondrial tricarboxylic acid cycle, oxidative phosphorylation, metabolite transport, and electrophysiology. J Biol Chem 282:24525-37.

ยป Open Access

Wu F, Yang F, Vinnakota KC, Beard DA (2007) J Biol Chem

Abstract: 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.

โ€ข Bioblast editor: Komlodi T

Cited by

  • Komlรณdi T, Cardoso LHD, Doerrier C, Moore AL, Rich PR, Gnaiger E (2021) Coupling and pathway control of coenzyme Q redox state and respiration in isolated mitochondria. Bioenerg Commun 2021.3. https://doi.org/10.26124/bec:2021-0003


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