API XML

Aop: 264

AOP Title

?


Uncoupling of oxidative phosphorylation leading to growth inhibition (2)

Short name:

?

Uncoupling of OXPHOS leading to growth inhibition (2)

Graphical Representation

?

Click to download graphical representation template

W1siziisijiwmjavmtevmjqvnnblm2xkbjl2mv9bt1aynjquanbnil0swyjwiiwidgh1bwiilci1mdb4ntawil1d?sha=d61cf031f5a5ec67

Authors

?


You Song

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

Point of Contact

?


You Song   (email point of contact)

Contributors

?


  • You Song

Status

?

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 Do not cite Under Development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

?

Revision dates for related pages

Page Revision Date/Time
Decrease, Coupling of oxidative phosphorylation November 27, 2020 14:49
Decrease, ATP synthase activity November 02, 2020 05:39
Decrease, Adenosine triphosphate November 27, 2020 17:10
Decrease, Plasma membrane ATPase activity November 02, 2020 05:48
Increase, Abnormal osmoregulation November 02, 2020 05:49
Increase, Tissue/organ damage November 02, 2020 05:49
Decrease, Growth November 27, 2020 17:27
Decrease, Coupling of OXPHOS leads to Decrease, ATP synthase activity November 02, 2020 05:41
Decrease, ATP synthase activity leads to Decrease, ATP November 02, 2020 05:41
Decrease, ATP leads to Decrease, ATPase activity November 02, 2020 05:50
Decrease, ATPase activity leads to Increase, Abnormal osmoregulation November 02, 2020 05:51
Increase, Abnormal osmoregulation leads to Increase, Tissue/organ damage November 02, 2020 05:51
Increase, Tissue/organ damage leads to Decrease, Growth November 02, 2020 05:42

Abstract

?


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


Background (optional)

?


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

?


Events: Molecular Initiating Events (MIE)

?

Key Events (KE)

?

Adverse Outcomes (AO)

?

Sequence Type Event ID Title Short name
MIE 1446 Decrease, Coupling of oxidative phosphorylation Decrease, Coupling of OXPHOS
KE 1808 Decrease, ATP synthase activity Decrease, ATP synthase activity
KE 1771 Decrease, Adenosine triphosphate Decrease, ATP
KE 1810 Decrease, Plasma membrane ATPase activity Decrease, ATPase activity
KE 1768 Increase, Abnormal osmoregulation Increase, Abnormal osmoregulation
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)

?

Title Adjacency Evidence Quantitative Understanding
Decrease, Coupling of OXPHOS leads to Decrease, ATP synthase activity adjacent High
Decrease, ATP synthase activity leads to Decrease, ATP adjacent High
Decrease, ATP leads to Decrease, ATPase activity adjacent
Decrease, ATPase activity leads to Increase, Abnormal osmoregulation adjacent
Increase, Abnormal osmoregulation leads to Increase, Tissue/organ damage adjacent
Increase, Tissue/organ damage leads to Decrease, Growth adjacent

Network View

?

 

Stressors

?

Life Stage Applicability

?

Taxonomic Applicability

?

Sex Applicability

?

Overall Assessment of the AOP

?



Domain of Applicability

?


Essentiality of the Key Events

?


Evidence Assessment

?


Quantitative Understanding

?


Considerations for Potential Applications of the AOP (optional)

?



References

?