How to deal with oxygen radicals stemming from mitochondrial fatty acid oxidation

Abstract

Oxygen radical formation in mitochondria is an incompletely understood attribute of eukaryotic cells. Recently, a kinetic model was proposed, in which the ratio between electrons entering the respiratory chain via FADH2 orNADHdetermines radical formation.During glucose breakdown, the ratio is low; during fatty acid breakdown, the ratio is high (the ratio increasing-asymptotically-with fatty acid length to 0.5,when comparedwith 0.2 for glucose). Thus, fatty acid oxidation would generate higher levels of radical formation. As a result, breakdown of fatty acids, performed without generation of extra FADH2 in mitochondria, could be beneficial for the cell, especially in the case of long and very long chained ones. This possibly has been a major factor in the evolution of peroxisomes. Increased radical formation, as proposed by the model, can also shed light on the lack of neuronal fatty acid oxidation and tells us about hurdles during early eukaryotic evolution. We specifically focus on extending and discussing the model in light of recent publications and findings. © 2014 The Author(s) Published by the Royal Society. All rights reserved.