Electron Transport System (ETS)

Most mitochondrial reactive oxygen species (ROS) originate from the electron transport system (ETS). The ETS normally produces ROS at lows rates. However, electron flow patterns can drastically alter when physiological conditions change causing ROS levels to surge. This is possible because all the complexes except for complex IV are physiologically reversible. To date, we are missing the information required to quantitatively predict these flow patterns and how they change in different physiological environments. To fill this need, we utilize our current ETS-ROS models and update with new data focused on understanding these flows and what controls them.

We hypothesize that the electron flow patterns in the ETS are regulated by the NAD+ and ubiquinone (Q) redox poise and the mitochondrial membrane potential (ΔΨ). Normally, redox sites embedded in protein complexes are protected against promiscuous reactions; however, some are exposed to the external environment at electron transfer sites caused by mutations, misfolded protein components, or injury. From this, we can perceive that protein-mediated mitochondrial ROS production is a simple matter of 1) having an electron source, 2) having a path from which electrons can traverse through protein complexes, and 3) available redox site(s) on the complex exposed to electron acceptors. We will evaluate these concepts with novel experimental data spanning biological spatial scales and construct a predictive computer model recapitulating the system behavior.