Altered content and fatty acid composition in cardiolipin
of mitochondria from mtDNA mutator mice

M. Vyssokikh1, I. Shabalina2,
A. Trifunovic3, B. Cannon2, V. Skulachev1,
J. Nedergaard2

1Belozersky Institute of Physico-Chemical Biology, Moscow State University, Vorobyevy Gory 1, Moscow 119991, Russia
2The Wenner-Gren Institute, the Arrhenius Laboratories F3, Stockholm University, SE-706 91 Stockholm, Sweden
3Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Germany

We have recently demonstrated that the assembly and turnover of the mitochondrial respiratory chain complexes I, III and IV, (but not complexes II and V) are altered in mitochondria from mtDNA mutator mice [1]. Since it is known that cardiolipin is essential for assembly and stability of respiratory chain complexes, we studied this phospholipid in mitochondria from mtDNA mutator mice. The content of mitochondrial phospholipids was analysed by two-dimensional high performance thin layer chromatography (2D-HPTLC). Content of cardiolipin was found significantly lower in liver and skeletal muscle mitochondria from mtDNA mutator mice as compared with wild-type mitochondria. To analyse fatty acid composition of cardiolipin, gas chromatography/flame ionization detection or electron ionization - mass spectrometry (GC/FID or El MS) was applied. Content of n6 fatty acids were remarkable lowered in cardiolipin from skeletal muscle and liver mitochondria of mtDNA mutator mice as compared with wild-type mice. As to content of saturated fatty acids, it was increased. Mitochondrial phospholipids were also studied in mice chronically treated with SkQ1, mitochondria-targeted plastoquinone linked by decane to triphenyl phosphonium cation. Content of cardiolipin was significantly increased in both wild-type and mtDNA mutator mitochondria. Alteration in fatty acid composition of cardiolipin from mtDNA mutator mitochondria was reversed after treatment with SkQ1. It consisted in an increase in the amount of 6n polyunsaturated fatty acids and in decrease in amount of saturated fatty acids.

[1] D. Edgar, I. Shabalina, Y. Camara, A. Wredenberg, M.A. Calvaruso, L. Nijtmans, J. Nedergaard, B. Cannon, N.G. Larsson, A. Trifunovic, Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice, Cell. Metab. 10 (2009) 131-138.

Homo Sapiens Liberatus Workshop, Moscow State University, May 2010