Rotenone is a mitochondrial complex I inhibitor with a likely causal association to a Parkinsonian phenotype in both humans and rodent models. Despite existing epidemiological and toxicological studies, the mechanistic link between rotenone exposure and neuronal damage remains unclear. SH-SY5Y neuroblastoma cells exposed to rotenone exhibited a perturbed metabolome. Absolute quantification by stable isotope dilution-liquid chromatography-mass spectrometry (SID-LC-MS) of coenzyme A (CoA) intermediates of fatty acid �-oxidation shows that acetyl- and palmitoyl-CoA levels are maintained. However, medium chain acyl-CoAs are subject to large decreases. Rotenone also induces increased glutamine utilization for fatty acid synthesis, a portion of which is through reductive carboxylation. Isotopic tracer experiments suggest lipid cycling may be responsible for these changes. Levels of palmitoylcarnitine were measured through SID-LC-MS and are increased in response to rotenone, indicating an increase in fatty acid import. Our findings indicate that the observed changes to lipid metabolism may play an important compensatory role in response to complex I inhibition by rotenone.

Rotenone causes alterations to lipid metabolism in SH-SY5Y cells

248th National Meeting (2014)

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