LC/MS characterization of rotenone induced cardiolipin oxidation in human lymphocytes: Implications for mitochondrial dysfunction associated with Parkinson's disease
Article first published online: 3 MAY 2013
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Special Issue: Lipidomics: Approaches and Applications in Nutrition Research
Volume 57, Issue 8, pages 1410–1422, August 2013
How to Cite
Tyurina, Y. Y., Winnica, D. E., Kapralova, V. I., Kapralov, A. A., Tyurin, V. A. and Kagan, V. E. (2013), LC/MS characterization of rotenone induced cardiolipin oxidation in human lymphocytes: Implications for mitochondrial dysfunction associated with Parkinson's disease. Mol. Nutr. Food Res., 57: 1410–1422. doi: 10.1002/mnfr.201200801
- Issue published online: 2 AUG 2013
- Article first published online: 3 MAY 2013
- Manuscript Accepted: 27 FEB 2013
- Manuscript Revised: 26 FEB 2013
- Manuscript Received: 4 DEC 2012
- NIH. Grant Numbers: ES020693, HL70755, U19AIO68021
- NIOSH. Grant Number: OH008282
- Cardiolipin peroxidation;
- Mitochondrial dysfunction;
- Parkinson's disease biomarkers
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 lipidomics we characterized molecular species of cardiolipin (CL) and its oxidation/hydrolysis products formed early in apoptosis and associated with the rotenone-induced mitochondrial dysfunction.
The major oxidized CL species – tetra-linoleoyl-CL – underwent oxidation to yield epoxy-C18:2 and dihydroxy-C18:2 derivatives predominantly localized in sn-1 and sn-2 positions, respectively. In addition, accumulation of mono-lyso-CL species and oxygenated free C18:2 were detected in rotenone-treated lymphocytes. These oxidation/hydrolysis products may be useful for the development of new biomarkers of mitochondrial dysfunction.