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Oxygen radicals shaping evolution: Why fatty acid catabolism leads to peroxisomes while neurons do without it

FADH2/NADH flux ratios determining mitochondrial radical formation were crucial for the eukaryotic invention of peroxisomes and catabolic tissue differentiation

Authors

  • Dave Speijer

    Corresponding author
    1. Academic Medical Centre (AMC), Department of Medical Biochemistry, University of Amsterdam, Amsterdam, The Netherlands
    • Academic Medical Centre (AMC), Department of Medical Biochemistry, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
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Abstract

Oxygen radical formation in mitochondria is a highly important, but incompletely understood, attribute of eukaryotic cells. I propose a kinetic model in which the ratio between electrons entering the respiratory chain via FADH2 or NADH is a major determinant in radical formation. During the breakdown of glucose, this ratio is low; during fatty acid breakdown, this ratio is much higher. The longer the fatty acid, the higher the ratio and the higher the level of radical formation. This means that very long chain fatty acids should be broken down without generation of FADH2 for mitochondria. This is accomplished in peroxisomes, thus explaining their role and evolution. The model explains many recent observations regarding radical formation by the respiratory chain. It also sheds light on the reasons for the lack of neuronal fatty acid (beta-) oxidation and for beneficial aspects of unsaturated fatty acids. Last but not least, it has very important implications for all models describing eukaryotic origins.

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