
This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Aop: 268
Title
Uncoupling of oxidative phosphorylation leading to growth inhibition via increased protein oxidation
Short name
Graphical Representation
Point of Contact
Contributors
- You Song
- Agnes Aggy
Status
Author status | OECD status | OECD project | SAAOP status |
---|---|---|---|
Under development: Not open for comment. Do not cite | Under Development | 1.92 | Included in OECD Work Plan |
This AOP was last modified on May 08, 2022 11:33
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Decrease, Coupling of oxidative phosphorylation | May 28, 2021 07:59 |
Decrease, Growth | November 28, 2020 15:07 |
Increase, Oxygen consumption | December 04, 2020 15:29 |
Increase, Reactive Oxygen Species production | April 11, 2021 18:03 |
Increase, Protein oxidation | April 30, 2020 12:37 |
Increase, Cell death | September 06, 2021 07:39 |
Decrease, Coupling of OXPHOS leads to Increase, Oxygen consumption | December 04, 2020 15:30 |
Increase, Oxygen consumption leads to Increase, ROS production | December 04, 2020 15:31 |
Increase, ROS production leads to Increase, Protein oxidation | April 30, 2020 12:38 |
Increase, Protein oxidation leads to Increase, Cell death | December 04, 2020 15:44 |
Increase, Cell death leads to Decrease, Growth | December 04, 2020 15:14 |
Abstract
The proposed project aims to develop a network of AOPs for mitochondrial uncoupler mediated adverse effects on aquatic organisms.
Background (optional)
The mitochondrion is central for diverse types of physiological processes, such as energy production, cell cycle regulation, lipid metabolism and ion homeostasis. Mitochondrial dysfunction has frequently been reported as a common (eco)toxicological effect induced by a wide range of environmental stressors through direct or indirect modes of action (Meyer et al., 2013). Chemical mediated mitochondrial dysfunctions are tightly associated with various diseases in human, such as neurodegeneration, cardiovascular malfunction, diabetes and cancer, and multiple types of effects in wildlife, such as metabolic disorders, growth arrest, developmental abnormalities, reproduction failure, mortality and population decline (Meyer et al., 2013). Several mitochondrial dysfunction related MIEs have been well characterized, such as uncoupling of oxidative phosphorylation (OXPHOS) and inhibition of specific protein complexes in the mitochondrial electron transport chain. These MIEs commonly affect the mitochondrial membrane potential and ATP synthetic processes, induce reactive oxygen species (ROS) and oxidative damage to DNA, protein and lipid, modulate plasma membrane ion transporter activities and trigger programmed cell death.
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Sequence | Type | Event ID | Title | Short name |
---|
MIE | 1446 | Decrease, Coupling of oxidative phosphorylation | Decrease, Coupling of OXPHOS |
KE | 1826 | Increase, Oxygen consumption | Increase, Oxygen consumption | |
KE | 257 | Increase, Reactive Oxygen Species production | Increase, ROS production | |
KE | 1767 | Increase, Protein oxidation | Increase, Protein oxidation | |
KE | 1825 | Increase, Cell death | Increase, Cell death |
AO | 1521 | Decrease, Growth | Decrease, Growth |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
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