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Event: 1840

Key Event Title

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

Inhibition, cytochrome oxidase

Short name

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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
Molecular

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

Cell term
cell

Organ term

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

Process	Object	Action
cytochrome-c oxidase activity	mitochondrion	decreased

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
Cytochrome oxidase inhibition leading to increased nasal lesions	MolecularInitiatingEvent	Katy Goyak (send email)	Under development: Not open for comment. Do not cite
Inhibition, cytochrome oxidase leads to Increased, pulmonary edema	MolecularInitiatingEvent	John Frisch (send email)	Under development: Not open for comment. Do not cite
Inhibition, cytochrome oxidase leads to Loss of olfactory function	MolecularInitiatingEvent	John Frisch (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

Term	Scientific Term	Evidence	Link
rodents	rodents	High	NCBI
humans	Homo sapiens	High	NCBI

Life Stages

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

Life stage	Evidence
All life stages	High

Sex Applicability

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

Term	Evidence
Unspecific	High

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

Cytochrome oxidase is an enzyme involved in the electron transport chain in generating adenosine triphosphate (ATP) in mitochondria as complex IV (Ricci et al. 2003; Kann and Kovacs 2007). Cytochrome oxidase is multimeric with many subunits (13 in mammals; 12 in some other organisms; Castresana et al. 1994; Barrientos et al. 2002). Inhibition of cytochrome oxidase leads to loss of mitochondrial energy production (Ricci et al. 2003; Liang et al. 2006).

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

Inhibition of cytochrome oxidase is measured by spectrophotometry (Miro et al. 1998), histochemistry (Melendez-Ferro et al. 2013), and commercially available enzyme assays (e.g., Sigma-Aldrich CYTOCOX1; Abcam ab239711; Abnova KA6690). Mention of trade names or commercial products does not constitute endorsement or recommendation for use.

Domain of Applicability

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

Life Stage: Applies to all life stages.

Sex: Applies to both males and females.

Taxonomic: Primarily studied in humans and laboratory rodents. Plausible for all eukaryotes, as well as some bacteria and archaea (Castresana et al. 1994).

References

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

Barrientos, A., Barros, M.H., Valnot, I., Rotig, A., Rustin, P., and Tzagoloff, A. Cytochrome oxidase in health and disease. Gene. 286(1):53-63.

Castresana, J., Lubben, M., Saraste, M., and Higgins, D.G. 1994. Evolution of cytochrome oxidase, an enzyme older than atmospheric oxygen. The EMBO Journal. 13 (11): 2516–2525.

Kann, O. and Kovacs R. 2007. Mitochondria and neuronal activity. American Journal of Physiology - Cell Physiology 292(2): C641–C657.

Liang, H.L., Whelan, H.T., Eells, J.T., Meng, H., Buchmann, E., Lerch-Gaggl, A., and Wong-Riley, M. 2006. Photobiomodulation partially rescues visual cortical neurons from cyanide-induced apoptosis. Neuroscience. 139(2): 639–649.

Melendez-Ferro, M., Rice, M.W., Roberts, R.C., and Perez-Costas, E. 2013. An accurate method for the quantification of cytochrome C oxidase in tissue sections. Journal of Neuroscience Methods. 214(2): 156-162.

Miro, O., Cardellach, F., Barrientos, A., Casademont, J., Rotig, A., and Rustin, P. 1998. Cytochrome c oxidase assay in minute amounts of human skeletal muscle using single wavelength spectrophotometers. Journal of Neuroscience Methods 80: 107–111.

Ricci, J.E., Waterhouse, N., Green, D.R. 2003. Mitochondrial functions during cell death, a complex (I-V) dilemma. Cell Death and Differentiation 10(5): 488–492.

NOTE: Italics indicate edits from John Frisch March 2025. A full list of updates can be found in the Change Log on the View History page.