A Model of Mitochondria in the Rat Hepatocyte

Abstract

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.