Biology subjects

Bell, W.

Publications and source records attributed to Bell, W..

3 recordsLinked to original sources

bioRxiv2022

A Complete Set of Equations and Parameters for the Computational Model of Mitochondrial Function for the Proximal Convoluted Tubule and Medullary Thick Ascending Limb Cells in the Rat Kidney

To investigate mitochondrial function of renal epithelial cells under different tissue oxygenation levels, we have developed and applied computational models of mitochondrial function of the proximal convoluted tubule and medullary thick ascending limb cells. The models predict several key cellular quantities, including ATP generation, P/O (phosphate/oxygen) ratio, proton motive force, electrical potential gradient, oxygen consumption, the redox state of important electron carriers, and ATP consumption. The complete set of model equations and parameters are presented here, together with local and global sensitivity analysis results.

cell biology↗

bioRxiv2021

A Mathematical Model of Mitochondria in Proximal Tubule and Thick Ascending Limb Cells

Mitochondria are a key player in several kinds of tissue injury, and are even the ultimate cause of certain diseases. In this work we introduce new models of mitochondrial ATP generation in multiple tissues, including liver hepatocytes and the medullary thick ascending limb in the kidney. Using this model, we predict these tissues responses to hypoxia, uncoupling, ischemia-reperfusion, and oxidative phosphorylation dysfunction. Our results suggest mechanisms explaining differences in robustness of mitochondrial function across tissues.The medullary thick ascending limb and proximal tubule in the kidney both experience a high metabolic demand, while having lower baseline activity of oxidative phosphorylation relative to the liver. These factors make these tissues susceptible to dysfunction of ComplexIII. A lower baseline oxygen tension observed in the thick ascending limb makes it susceptible to Complex IV. On the other hand, since the liver lacks these risk factors, and has higher baseline rates of glycolysis, it is less susceptible to all kinds of oxidative phosphorylation dysfunction.

physiology↗

bioRxiv2021

A Model of Mitochondria in the Rat Hepatocyte

Mitochondria are a key player in several kinds of tissue injury, and are even the ultimate cause of certain diseases. In this work we introduce a new model of mitochondrial ATP generation in liver hepatocytes of the rat. Ischemia-reperfusion is an intriguing example of a non-equilibrium behaviour driven by a change in tissue oxygen tension. Ischemia involves prolonged hypoxia, followed by the sudden return of oxygen during reperfusion. During reperfusion, we predict that the build up of succinate causes the electron transport chain in the liver to temporarily be in a highly reduced state. This can lead to the production of reactive oxygen species. We accurately predict the timescale on which the electron transport chain is left in a reduced state, and we observe levels of reduction likely to lead to reactive oxygen species production. Aside from the above, we predict thresholds for ATP depletion from hypoxia, and we predict the consequences for oxygen consumption of uncoupling.

physiology↗