API

Relationship: 1780

Title

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Mitochondrial Complex I inhibition leads to Decrease in mitochondrial oxidative phosphorylation

Upstream event

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Mitochondrial Complex I 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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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 I, III or IV.

Inhibition of complex I, III or IV leads to a reduction in proton gradient and therefore impair or completely prevent the production of mitochondrial membrane dependent ATP production.

 

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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