API XML

Aop: 265

AOP Title

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Uncoupling of oxidative phosphorylation leading to growth inhibition (3)

Short name:

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Uncoupling of OXPHOS leading to growth inhibition (3)

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 Do not cite Under Development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 25, 2020 05:49

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Revision dates for related pages

Page Revision Date/Time
Decrease, Coupling of oxidative phosphorylation November 27, 2020 14:49
Increase, Mitochondrial complex III dysfunction November 02, 2020 05:56
Increase, Cytochrome c release November 02, 2020 05:57
Increase, Apoptosis April 15, 2017 16:17
Increase, Tissue/organ damage November 02, 2020 05:49
Decrease, Growth November 28, 2020 15:07
Decrease, Coupling of OXPHOS leads to Increase, Complex III dysfunction November 02, 2020 05:58
Increase, Complex III dysfunction leads to Increase, Cyt c release November 02, 2020 05:59
Increase, Cyt c release leads to Increase, Apoptosis November 02, 2020 05:59
Increase, Apoptosis leads to Increase, Tissue/organ damage November 02, 2020 05:59
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 1811 Increase, Mitochondrial complex III dysfunction Increase, Complex III dysfunction
KE 1812 Increase, Cytochrome c release Increase, Cyt c release
KE 1365 Increase, Apoptosis Increase, 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 III dysfunction adjacent
Increase, Complex III dysfunction leads to Increase, Cyt c release adjacent
Increase, Cyt c release leads to Increase, Apoptosis adjacent High
Increase, 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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Life stage Evidence
Not Otherwise Specified
All life stages Not Specified

Taxonomic Applicability

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Sex Applicability

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Sex Evidence
Unspecific Not Specified

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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