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Publication Detail

Title: Inhibition of neuronal cell mitochondrial complex I with rotenone increases lipid β-oxidation, supporting acetyl-coenzyme A levels.

Authors: Worth, Andrew J; Basu, Sankha S; Snyder, Nathaniel W; Mesaros, Clementina; Blair, Ian A

Published In J Biol Chem, (2014 Sep 26)

Abstract: Rotenone is a naturally occurring mitochondrial complex I inhibitor with a known association with parkinsonian phenotypes in both human populations and rodent models. Despite these findings, 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 levels of acetyl-CoA were found to be maintained despite a significant decrease in glucose-derived acetyl-CoA. Furthermore, palmitoyl-CoA levels were maintained, whereas the levels of many of the medium-chain acyl-CoA species were significantly reduced. Additionally, using isotopologue analysis, we found that β-oxidation of fatty acids with 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 that alterations to lipid and glutamine metabolism play an important compensatory role in response to complex I inhibition by rotenone.

PubMed ID: 25122772 Exiting the NIEHS site

MeSH Terms: Acetyl Coenzyme A/metabolism*; Cell Line, Tumor; Electron Transport Complex I/antagonists & inhibitors*; Electron Transport Complex I/metabolism; Fatty Acids/metabolism*; Glutamine/metabolism; Humans; Neurons; Oxidation-Reduction/drug effects; Palmitoyl Coenzyme A/metabolism*; Rotenone/pharmacology*; Uncoupling Agents/pharmacology*

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