API XML

Aop: 268

AOP Title

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Uncoupling of oxidative phosphotylation leading to growth inhibition (6)

Short name:

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Uncoupling of OXPHOS leading to reproduction decline (6)

Graphical Representation

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Click to download graphical representation template

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Authors

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You Song

Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, NO-0349 Oslo, Norway

Point of Contact

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You Song   (email point of contact)

Contributors

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  • You Song

Status

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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 Do not cite Under Development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 November 02, 2020 06:23

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Revision dates for related pages

Page Revision Date/Time
Decrease, Coupling of oxidative phosphorylation November 20, 2020 13:47
Increase, Mitochondrial complex I dysfunction November 02, 2020 06:15
Increase, Reactive oxygen species production September 16, 2017 10:14
Increase, Oxidative DNA damage March 19, 2019 09:40
Apoptosis February 10, 2020 03:23
Increase, Tissue/organ damage November 02, 2020 05:49
Decrease, Growth October 07, 2020 15:26
Decrease, Coupling of OXPHOS leads to Increase, Complex I dysfunction November 02, 2020 06:17
Increase, Complex I dysfunction leads to Increase, ROS production November 02, 2020 06:17
Increase, ROS production leads to Increase,Oxidative DNA damage April 30, 2020 13:53
Increase,Oxidative DNA damage leads to Apoptosis November 02, 2020 06:23
Apoptosis leads to Increase, Tissue/organ damage November 02, 2020 06:23
Increase, Tissue/organ damage leads to Decrease, Growth November 02, 2020 05:42

Abstract

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The proposed project aims to develop a network of AOPs for mitochondrial uncoupler mediated adverse effects on aquatic organisms.


Background (optional)

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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

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Events: Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

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Sequence Type Event ID Title Short name
MIE 1446 Decrease, Coupling of oxidative phosphorylation Decrease, Coupling of OXPHOS
KE 1813 Increase, Mitochondrial complex I dysfunction Increase, Complex I dysfunction
KE 257 Increase, Reactive oxygen species production Increase, ROS production
KE 1608 Increase, Oxidative DNA damage Increase,Oxidative DNA damage
KE 1262 Apoptosis Apoptosis
KE 1809 Increase, Tissue/organ damage Increase, Tissue/organ damage
AO 1521 Decrease, Growth Decrease, Growth

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Decrease, Coupling of OXPHOS leads to Increase, Complex I dysfunction adjacent
Increase, Complex I dysfunction leads to Increase, ROS production adjacent
Increase, ROS production leads to Increase,Oxidative DNA damage adjacent
Increase,Oxidative DNA damage leads to Apoptosis adjacent
Apoptosis leads to Increase, Tissue/organ damage adjacent
Increase, Tissue/organ damage leads to Decrease, Growth adjacent

Network View

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Stressors

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Life Stage Applicability

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Taxonomic Applicability

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Sex Applicability

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Overall Assessment of the AOP

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Domain of Applicability

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Essentiality of the Key Events

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Evidence Assessment

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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