To the extent possible under law, AOP-Wiki has waived all copyright and related or neighboring rights to KE:1477
Key Event Title
Decrease, Oxidative phosphorylation
|Level of Biological Organization|
Key Event Components
Key Event Overview
AOPs Including This Key Event
|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 Do not cite|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 Do not cite|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 Do not cite|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 Do not cite|
Key Event Description
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
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
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).