Inhibition of neuronal cell mitochondrial complex I with rotenone increases lipid {beta}-oxidation supporting acetyl-coenzyme A levels [Metabolism]

August 12th, 2014 by Worth, A. J., Basu, S. S., Snyder, N. W., Mesaros, C., Blair, I. A.

Rotenone is a naturally occurring mitochondrial complex I inhibitor with a known association to Parkinsonian phenotypes in both human populations and rodent models. Despite this finding, a clear mechanistic link between rotenone exposure and neuronal damage remains to be determined. Here, we report alterations to lipid metabolism in SH-SY5Y neuroblastoma cells exposed to rotenone. The absolute intracellular concentrations of acetyl-coenzyme A were found to be maintained in spite of a significant decrease in glucose derived acetyl-coenzyme A (CoA). Furthermore, palmitoyl-CoA levels were maintained, whereas, levels of many of the medium chain acyl-Coenzyme A species were significantly reduced. Additionally, using isotopologue analysis it was found that β-oxidation of fatty acids of varying chain lengths helped maintain acetyl-CoA levels. Rotenone also induced increased glutamine utilization for lipogenesis, in part through reductive carboxylation as has been found previously in other cell types. Finally, palmitoylcarnitine levels were increased in response to rotenone, indicating an increase in fatty acid import. Taken together, these findings show alterations to lipid and glutamine metabolism play an important compensatory role in response to complex I inhibition by rotenone.
  • Posted in Journal of Biological Chemistry, Publications
  • Comments Off on Inhibition of neuronal cell mitochondrial complex I with rotenone increases lipid {beta}-oxidation supporting acetyl-coenzyme A levels [Metabolism]