This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Uncoupling of oxidative phosphorylation leading to growth inhibition (2)
- You Song
|Author status||OECD status||OECD project||SAAOP status|
|Under development: Not open for comment. Do not cite||Under Development|
This AOP was last modified on December 04, 2020 15:14
|Decrease, Coupling of oxidative phosphorylation||December 07, 2020 06:41|
|Decrease, Adenosine triphosphate pool||November 29, 2020 16:12|
|Decrease, Growth||November 28, 2020 15:07|
|Increase, Cell death||December 04, 2020 15:13|
|Decrease, Coupling of OXPHOS leads to Decrease, ATP pool||December 07, 2020 07:25|
|Decrease, ATP pool leads to Increase, Cell death||December 04, 2020 15:13|
|Increase, Cell death leads to Decrease, Growth||December 04, 2020 15:14|
The proposed project aims to develop a network of AOPs for mitochondrial uncoupler mediated adverse effects on aquatic organisms.
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
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Relationships Between Two Key Events (Including MIEs and AOs)
|Decrease, Coupling of OXPHOS leads to Decrease, ATP pool||adjacent|
|Decrease, ATP pool leads to Increase, Cell death||adjacent|
|Increase, Cell death leads to Decrease, Growth||adjacent|