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).
Available from December 15, 2022
In series:OECD Series on Adverse Outcome Pathwaysview more titles