Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 57, Issue 8, Pages 1410-1422Publisher
WILEY
DOI: 10.1002/mnfr.201200801
Keywords
Apoptosis; Cardiolipin peroxidation; Lymphocytes; Mitochondrial dysfunction; Parkinson's disease biomarkers
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Funding
- NIH [ES020693, HL70755, U19AIO68021]
- NIOSH [OH008282]
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Scope: Rotenone is a toxicant believed to contribute to the development of Parkinson's disease. Methods and results: Using human peripheral blood lymphocytes we demonstrated that exposure to rotenone resulted in disruption of electron transport accompanied by the production of reactive oxygen species, development of apoptosis and elevation of peroxidase activity of mitochondria. Employing LC/MS-based lipidomics/oxidative lipidomicswe characterized molecular species of cardiolipin (CL) and its oxidation/hydrolysis products formed early in apoptosis and associated with the rotenone-induced mitochondrial dysfunction. Conclusion: The major oxidized CL species -tetra-linoleoyl-CL -underwent oxidation to yield epoxy-C-18:2 and dihydroxy-C-18:2 derivatives predominantly localized in sn-1 and sn-2 positions, respectively. In addition, accumulation of mono-lyso-CL species and oxygenated free C-18:2 were detected in rotenone-treated lymphocytes. These oxidation/hydrolysis products may be useful for the development of new biomarkers of mitochondrial dysfunction.
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