Upstream eventMitochondrial Complex IV inhibition
Increased reactive oxygen species (in the mitochondria)
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding|
|Mitochondrial complex inhibition leading to liver injury||adjacent||Moderate||Moderate|
Life Stage Applicability
Key Event Relationship Description
Perturbation of one of the complexes in the oxidative phosphorylation will lead to disturbed electron flow and therefore more available electron that can create oxygen radicals.
Threshold relationship = When the radical formation reaches a certain threshold the antioxidant system cannot cope with the inflow of radicals leading to accumulation of radicals in the mitochondria. One of the important antioxidants involved in the ROS removal is MnSOD.
Evidence Supporting this KER
It has been well established that complex inhibition leads to ROS production.
Mitochondrial complexes possess multiple sites that can produce these superoxides.