Inhibition, ETC complexes of the respiratory chain leads to Increase, Oxidative Stress

1. One of the articles, the Shaki et al.’s 2012 article, did not show dose concordance for this KER when using uranium as a treatment, as oxidative stress was induced before mitochondrial electron transport chain inhibition occurred, at 50 and 100 μM respectively.

There are currently no articles detailing the response-response relationship between the inhibition of the mitochondrial ETC and an increase in oxidative stress. Further studies will need to be conducted in order to determine a response-response relationship.

There are currently not enough articles which investigate the time-scale over which inhibition of the mitochondrial ETC occurs and instigates oxidative stress and further research must therefore be conducted to identify the time-scale for this relationship.

There is a known feedback loop which influences this key event relationship. Inhibition of the mitochondrial electron transport chain results in increased oxidative stress, which in turn further inhibits the mitochondrial electron transport chain (Guo et al., 2013). The molecular basis behind this is that the ROS molecules are damaging to the macromolecules, such as DNA, proteins, and lipids that they interact with in the mitochondria (Guo et al., 2013). Unrepaired damage to mitochondrial DNA, which is known to be more sensitive than nuclear DNA to ROS molecules due to proximity to the ETC, leads to defective complex I and III function and results in increased reduction of oxygen to it’s reactive forms (Guo et al., 2013; Gonzalez-Hunt et al., 2018). Similarly, damage to the mitochondrial DNA coding for other critical proteins for electron transport can lead to further generation of ROS molecules, all leading to a cycle of ROS molecule generation and organelle dysfunction which ultimately results in the induction of apoptosis (Guo et al., 2013).