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Papers In Press, published online ahead of print November 1, 2008
J. Lipid Res., doi:10.1194/jlr.M800168-JLR200

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Journal of Lipid Research, Vol. 49, 2427-2440, November 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

siRNA screening reveals JNK2 as an evolutionary conserved regulator of triglyceride homeostasis

Vinciane Grimard^*, Julia Massier^*, Doris Richter^*, Dominik Schwudke^*, Yannis Kalaidzidis^*, Eugenio Fava^*, Albin Hermetter and Christoph Thiele^1,*

^* Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany
Institute of Biochemistry, Graz University of Technology, Petersgasse 12/II, A-8010 Graz, Austria

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of two figures and two tables.

Published, JLR Papers in Press, July 7, 2008.

C.T. and V.G. were supported by the German Research Foundation (Transregio TR13/D2) and J.M. was supported by the Boehringer Ingelheim Foundation.

¹ To whom correspondence should be addressed. e-mail: thiele{at}mpi-cbg.de

Lipid homeostasis is essential for proper function of cells and organisms. To unravel new regulators of this system, we developed a screening procedure, combining RNA interference in HeLa cells and TLC, which enabled us to monitor modifications of lipid composition resulting from short, interfering RNA knock-downs. We applied this technique to the analysis of 600 human kinases. Despite the occurrence of off-target effects, we identified JNK2 as a new player in triglyceride (TG) homeostasis and lipid droplet metabolism and, more specifically, in the regulation of lipolysis. Similar control of the level of TGs and lipid droplets was observed for its Schizosaccharomyces pombe homolog, Sty1, suggesting an evolutionary conserved function of mitogen-activated protein kinases in the regulation of lipid storage in eukaryotic cells.

Supplementary key words c-jun N-terminal kinase • HeLa cells • kinase • lipid droplet • mitogen-activated protein kinase-9

Abbreviations: ACAT, acyl-CoA:cholesterol acyltransferase; CE, cholesteryl ester; JNK, c-jun N-terminal kinase; MAPK, mitogen-activated protein kinase; RNAi, RNA interference; siRNA, short, interfering RNA; TG, triglyceride

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