This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Uncoupling of oxidative phosphorylation leading to growth inhibition via increased cell death
Point of Contact
- You Song
|Author status||OECD status||OECD project||SAAOP status|
|Open for citation & comment||Under Development||1.92||Included in OECD Work Plan|
This AOP was last modified on August 12, 2021 05:41
|Decrease, Coupling of oxidative phosphorylation||May 28, 2021 07:59|
|Decrease, Adenosine triphosphate pool||June 14, 2021 13:40|
|Decrease, Growth||November 28, 2020 15:07|
|Increase, Cell death||September 06, 2021 07:39|
|Decrease, Coupling of OXPHOS leads to Decrease, ATP pool||June 15, 2021 13:07|
|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|