API

Relationship: 1785

Title

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Mitochondrial Complex IV inhibition leads to Increased reactive oxygen species (in the mitochondria)

Upstream event

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Mitochondrial Complex IV inhibition

Downstream event

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Increased reactive oxygen species (in the mitochondria)

Key Event Relationship Overview

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AOPs Referencing Relationship

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AOP Name Adjacency Weight of Evidence Quantitative Understanding
Mitochondrial complex inhibition leading to liver injury adjacent Moderate Moderate

Taxonomic Applicability

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Sex Applicability

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Life Stage Applicability

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Key Event Relationship Description

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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

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Biological Plausibility

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It has been well established that complex inhibition leads to ROS production.

Mitochondrial complexes possess multiple sites that can produce these superoxides.

Empirical Evidence

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Uncertainties and Inconsistencies

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Quantitative Understanding of the Linkage

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Response-response Relationship

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Time-scale

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Known modulating factors

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Known Feedforward/Feedback loops influencing this KER

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Domain of Applicability

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References

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