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AOP: 273
Title
Mitochondrial complex inhibition leading to liver injury
Short name
Graphical Representation
Point of Contact
Contributors
- Wanda van der Stel
- Marvin Martens
Coaches
OECD Information Table
OECD Project # | OECD Status | Reviewer's Reports | Journal-format Article | OECD iLibrary Published Version |
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This AOP was last modified on April 29, 2023 16:03
Revision dates for related pages
Page | Revision Date/Time |
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Increase, Mitochondrial complex III antagonism | December 04, 2020 17:24 |
Mitochondrial Complex IV inhibition | March 07, 2019 05:15 |
Mitochondrial Complex V inhibition | March 07, 2019 05:21 |
Decrease in mitochondrial oxidative phosphorylation | December 19, 2018 09:36 |
Increased reactive oxygen species (in the mitochondria) | December 19, 2018 09:37 |
Mitochondrial Injury | December 19, 2018 09:37 |
Necrotic Tissue | March 07, 2019 04:19 |
Liver Injury | March 07, 2019 04:23 |
Binding of inhibitor, NADH-ubiquinone oxidoreductase (complex I) | March 28, 2018 04:51 |
Inhibition, NADH-ubiquinone oxidoreductase (complex I) | March 12, 2018 11:03 |
Impaired, Proteostasis | March 15, 2018 12:46 |
Increase, Cell injury/death | May 27, 2024 07:23 |
Binding of inhibitor to mitochondrial complex III | June 07, 2019 09:31 |
Binding of inhibitor to mitochondrial complex IV | June 07, 2019 09:31 |
Binding of inhibitor to mitochondrial complex V | June 07, 2019 09:31 |
Mitochondrial dysfunction | April 17, 2024 08:26 |
Increase, Mitochondrial complex III antagonism leads to Decrease in mitochondrial oxidative phosphorylation | March 07, 2019 08:37 |
Mitochondrial Complex IV inhibition leads to Decrease in mitochondrial oxidative phosphorylation | March 07, 2019 08:38 |
Mitochondrial Complex V inhibition leads to Decrease in mitochondrial oxidative phosphorylation | March 07, 2019 08:38 |
Necrotic Tissue leads to Liver Injury | March 07, 2019 06:07 |
Binding of inhibitor, NADH-ubiquinone oxidoreductase (complex I) leads to Inhibition, NADH-ubiquinone oxidoreductase (complex I) | August 25, 2017 09:35 |
Inhibition, NADH-ubiquinone oxidoreductase (complex I) leads to Decrease in mitochondrial oxidative phosphorylation | June 07, 2019 09:12 |
Impaired, Proteostasis leads to Cell injury/death | June 07, 2019 09:28 |
Cell injury/death leads to Necrotic Tissue | March 07, 2019 06:05 |
Binding of inhibitor, mitochondrial complex III leads to Increase, Mitochondrial complex III antagonism | June 07, 2019 09:31 |
Binding of inhibitor, mitochondrial complex IV leads to Mitochondrial Complex IV inhibition | June 07, 2019 09:32 |
Binding of inhibitor, mitochondrial complex V leads to Mitochondrial Complex V inhibition | June 07, 2019 09:32 |
Decrease in mitochondrial oxidative phosphorylation leads to Mitochondrial dysfunction | June 15, 2019 11:06 |
Increased reactive oxygen species (in the mitochondria) leads to Mitochondrial dysfunction | June 15, 2019 11:07 |
Mitochondrial dysfunction leads to Increased reactive oxygen species (in the mitochondria) | June 15, 2019 11:08 |
Mitochondrial dysfunction leads to Impaired, Proteostasis | August 25, 2017 08:35 |
Abstract
This AOP focusses on the inhibition of any of the mitochondrial complexes (I,II,III,IV or V) which eventually leads to the initiation of liver injury. In short, inhibition (fully or partially) of mitochondrial complexes that form the OXPHOS will lead to perturbation of the OXPHOS itself. OXPHOS perturbation will manifest as lower or no production of ATP via the mitochondria. Besides OXPHOS perturbation, the inhibition of the complexes will also lead to accumulation of the unused electrons and therefore ROS formation. Both process combined will trigger mitochondrial injury. One the most important additions to the AOPwiki by us would be to improve the mitochondrial injury key event with more detail, more method descriptions and more evidence. Finally when a certain threshold is reached mitochondria cannot coop with the induced stress and will trigger the cell death pathways (apoptosis and necrosis depending on ATP availability). Evidently, the cell death will proceed to necrotic tissue and in the end to liver injury.
AOP Development Strategy
Context
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
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MIE | 1542 | Increase, Mitochondrial complex III antagonism | Increase, Mitochondrial complex III antagonism |
MIE | 1543 | Mitochondrial Complex IV inhibition | Mitochondrial Complex IV inhibition |
MIE | 1544 | Mitochondrial Complex V inhibition | Mitochondrial Complex V inhibition |
MIE | 888 | Binding of inhibitor, NADH-ubiquinone oxidoreductase (complex I) | Binding of inhibitor, NADH-ubiquinone oxidoreductase (complex I) |
MIE | 887 | Inhibition, NADH-ubiquinone oxidoreductase (complex I) | Inhibition, NADH-ubiquinone oxidoreductase (complex I) |
MIE | 1653 | Binding of inhibitor to mitochondrial complex III | Binding of inhibitor, mitochondrial complex III |
MIE | 1654 | Binding of inhibitor to mitochondrial complex IV | Binding of inhibitor, mitochondrial complex IV |
MIE | 1655 | Binding of inhibitor to mitochondrial complex V | Binding of inhibitor, mitochondrial complex V |
KE | 1545 | Decrease in mitochondrial oxidative phosphorylation | Decrease in mitochondrial oxidative phosphorylation |
KE | 1546 | Increased reactive oxygen species (in the mitochondria) | Increased reactive oxygen species (in the mitochondria) |
KE | 1547 | Mitochondrial Injury | Mitochondrial Injury |
KE | 889 | Impaired, Proteostasis | Impaired, Proteostasis |
KE | 55 | Increase, Cell injury/death | Cell injury/death |
KE | 177 | Mitochondrial dysfunction | Mitochondrial dysfunction |
AO | 1548 | Necrotic Tissue | Necrotic Tissue |
AO | 1549 | Liver Injury | Liver Injury |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
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