OECD Series on Adverse Outcome Pathways
An Adverse Outcome Pathway (AOP) describes a logical sequence of causally linked events at different levels of biological organisation, which follows exposure to a stressor and leads to an adverse health effect in humans or wildlife. AOPs are the central element of a toxicological knowledge framework, promoted by member countries through OECD, built to support chemical risk assessment based on mechanistic reasoning. These AOPs are available in the AOP-Wiki, an interactive and virtual encyclopaedia for AOP development. Following their development and review, the endorsed AOPs are published in the OECD Series on Adverse Outcome Pathways. As scientific knowledge progresses, the publication of an AOP in this series does not preclude regular updates or new contributions to a given AOP. While the AOP-Wiki is a dynamic tool, only impactful changes to the AOP will be reflected in subsequent updates of the published AOP.
- ISSN: 2415170X (online)
- https://doi.org/10.1787/2415170X
Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation
This Adverse Outcome Pathway (AOP) describes the linkage between uncoupling of oxidative phosphorylation (OXPHOS) and growth inhibition via decreased cell proliferation. The mitochondrial OXPHOS machinery is a key physiological process responsible for producing the primary cellular energy, adenosine triphosphate (ATP). Uncoupling of OXPHOS is a well-known mechanism of action of many chemicals and can affect many ATP-dependent biological functions. Cell proliferation in particular, as a major process to achieve organismal growth, is positively correlated with the cellular ATP level and highly susceptible to energy depletion. This AOP causally links uncoupling of OXPHOS to growth inhibition, through ATP depletion and reduced cell proliferation with strong weight of evidence support. This AOP is of high regulatory relevance, as it is considered applicable to both human health and ecological risk assessments. The AOP also forms the core of a larger AOP network addressing uncoupling of OXPHOS mediated growth inhibition. This AOP is referred to as AOP 263 in the Collaborative Adverse Outcome Pathway Wiki (AOP-Wiki).
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