
This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Aop: 264
Title
Uncoupling of oxidative phosphorylation leading to growth inhibition via ATP depletion associated cell death
Short name
Graphical Representation
Point of Contact
Contributors
- You Song
Status
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 November 02, 2022 06:16
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Decrease, Coupling of oxidative phosphorylation | May 28, 2021 07:59 |
Decrease, Adenosine triphosphate pool | June 14, 2021 13:40 |
Cell injury/death | July 15, 2022 09:46 |
Decrease, Growth | July 06, 2022 07:36 |
Decrease, Coupling of OXPHOS leads to Decrease, ATP pool | July 06, 2022 07:39 |
Decrease, ATP pool leads to Cell injury/death | September 27, 2022 13:24 |
Cell injury/death leads to Decrease, Growth | September 27, 2022 13:22 |
Abstract
The proposed project aims to develop a network of AOPs for mitochondrial uncoupler mediated adverse effects on aquatic organisms.
AOP Development Strategy
Context
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.
Strategy
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Type | Event ID | Title | Short name |
---|
MIE | 1446 | Decrease, Coupling of oxidative phosphorylation | Decrease, Coupling of OXPHOS |
KE | 1771 | Decrease, Adenosine triphosphate pool | Decrease, ATP pool |
KE | 55 | Cell injury/death | Cell injury/death |
AO | 1521 | Decrease, Growth | Decrease, Growth |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
---|
Decrease, Coupling of OXPHOS leads to Decrease, ATP pool | adjacent | Moderate | Not Specified |
Decrease, ATP pool leads to Cell injury/death | adjacent | Moderate | Not Specified |
Cell injury/death leads to Decrease, Growth | adjacent | Moderate | Not Specified |
Network View
Prototypical Stressors
Life Stage Applicability
Taxonomic Applicability
Sex Applicability
Overall Assessment of the AOP
Domain of Applicability
Essentiality of the Key Events
Evidence Assessment
Known Modulating Factors
Modulating Factor (MF) | Influence or Outcome | KER(s) involved |
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