Rotenone induces reductive stress and triacylglycerol deposition in C2C12 cells

Quan He, Miao Wang, Christopher Petucci, Stephen J. Gardell, Xianlin Han

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Environmental rotenone is associated with Parkinson's disease due to its inhibitory property to the complex I of mitochondrial respiration chain. Although environmental pollution has been postulated as a causal factor for the increasing prevalence of obesity, the role of rotenone in the pathogenesis of obesity has not been studied. We employed muscle-derived cell C2C12 as a model and shotgun lipidomics as a tool for lipid analysis and found that treatment with rotenone led to the profound deposition of intracellular triacylglycerol (TAG) in a time- and dose-dependent fashion. The TAG deposition resulted from complex I inhibition. Further studies revealed that rotenone induced mitochondrial stress as shown by decreased mitochondrial oxygen consumption rate, increased NADH/NAD+ ratio (i.e., reductive stress) and mitochondrial metabolites. We demonstrated that rotenone activated fatty acid de novo synthesis and TAG synthesis and ultimately resulted in intracellular TAG deposition. These studies suggested that increased mitochondrial stresses might be an underlying mechanism responsible for TAG accumulation manifest in obesity.

Original languageEnglish (US)
Pages (from-to)2749-2755
Number of pages7
JournalInternational Journal of Biochemistry and Cell Biology
Volume45
Issue number12
DOIs
StatePublished - Oct 29 2013
Externally publishedYes

Keywords

  • ATP citrate lyase
  • Mitochondrial complex I
  • Obesity
  • Shotgun lipidomics
  • Triacylglycerol

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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