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Event: 1477

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Decrease, Oxidative phosphorylation

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Decrease, OXPHOS
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Cellular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
Reduction in photophosphorylation leading to growth inhibition in aquatic plants KeyEvent Arthur Author (send email) Under development: Not open for comment. Do not cite
Complex I inhibition leads to Fanconi syndrome KeyEvent Evgeniia Kazymova (send email) Under development: Not open for comment. Do not cite
Excessive ROS leading to mortality (2) KeyEvent Brendan Ferreri-Hanberry (send email) Under development: Not open for comment. Do not cite
ROS production leading to population decline via mitochondrial dysfunction KeyEvent Agnes Aggy (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

An indication of the the relevant sex for this KE. More help

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Oxidative phosphorylation is the process in which reducing equivalents (NADH, FADH2) produced from catabolism of carbohydrates or fatty acid are further metabolised in the mitochondrial electron transport chain (ETC) to produce ATP. This is done by a set of enzymes that responsible for building a proton gradient across the inner mitochondrial membrane that allows ATP production by the ATP synthase. When this chain is interrupted (e.g. interference by ROS, dissipation of the proton gradient, loss of integrity of the mitochondrial membranes), oxidative phosphorylation is decreased and ATP production by this means is impaired.

The dissipation of the proton gradient results in a loss of the highly negative mitochondrial membrane potential (MMP) and a depletion of ATP. When the ETC is blocked, a decrease in O2 consumption rate can also be observed, as O2 is consumed to pump the protons into the intermembrane space of the mitochondria.

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

The MMP can be studied with mitochondrial dyes (e.g. JC-1, rhodamine 123) (Sakamuru et al. 2012), extracellular lactate reflects an increase in glycolytic rate (colorimetric assay) which can compensate for the low ATP production in the mitochondria (Limonciel et al. 2011) and O2 consumption can now be finely measured using the Seahorse device from Agilent (Abe et al. 2010)

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

References

List of the literature that was cited for this KE description. More help

Abe, Yoshifusa et al. 2010. “Bioenergetic Characterization of Mouse Podocytes.” American Journal of Physiology. Cell Physiology 299(2):C464-76. Retrieved December 5, 2017 (http://www.ncbi.nlm.nih.gov/pubmed/20445170).

Limonciel, A. et al. 2011. “Lactate Is an Ideal Non-Invasive Marker for Evaluating Temporal Alterations in Cell Stress and Toxicity in Repeat Dose Testing Regimes.” Toxicology in Vitro 25(8).

Sakamuru, Srilatha et al. 2012. “Application of a Homogenous Membrane Potential Assay to Assess Mitochondrial Function.” Physiological Genomics 44(9):495–503. Retrieved December 5, 2017 (http://www.ncbi.nlm.nih.gov/pubmed/22433785).