API

Relationship: 1783

Title

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Mitochondrial Complex V inhibition leads to Decrease in mitochondrial oxidative phosphorylation

Upstream event

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Mitochondrial Complex V inhibition

Downstream event

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Decrease in mitochondrial oxidative phosphorylation

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 High High

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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The initiation event is the reversibly or irreversibly interaction to any of the subunits in the mitochondrial complex V.

Inhibition of complex IV directly prevents the production of ATP in the mitochondria , because the catalyzing element isn’t functional anymore.

Threshold relationship = The cell can cope with inhibition of the various mitochondrial complexes and the following decreased OXPHOS depending on the number of mitochondria affected. The more mitochondria within a cell are perturbed, the lower the concentration of available ATP will become. The cell can influence the threshold at which these low ATP levels will become lethal, for example by upregulating the number of available mitochondria (biogenesis).

Evidence Supporting this KER

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Biological Plausibility

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It is broadly accepted that complex inhibition leads to decreased mitochondrial oxidative phosphorylation.

Deficiencies in complex I in patient leads to decreased activity of the complex

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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