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A more recent version of this article appeared on January 1, 2006
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Submitted on June 9, 2005
Revised on September 15, 2005
Accepted on October 14, 2005
*Institute of Biochemistry, Graz University of Technology, 8010 Graz, Austria; Department of Medicine, Division of Biochemistry, University of Fribourg, 1700 Fribourg, Switzerland; Institute of Plant Sciences, Karl-Franzens University Graz, 8010 Graz, Austria
Monitoring Editor: Howard Riezman
The mechanisms that govern intracellular transport of sterols in eukaryotic cells are not well understood. S. cerevisiae is a facultative anaerobic organism that becomes auxotroph for sterols and unsaturated fatty acids in the absence of oxygen. To identify pathways that are required for uptake and transport of sterols, we performed a systematic screen of the yeast deletion mutant collection for genes that are required for growth under anaerobic conditions. Of the 
4800 nonessential genes represented in the deletion collection, 37 were essential for growth under anaerobic conditions. These affect a wide range of cellular functions, including biosynthetic pathways for certain amino acids and cofactors, reprogramming of transcription and translation, mitochondrial function and biogenesis, and membrane trafficking. 33 of these mutants failed to grow on lipid-supplemented media when combined with a mutation in HEM1, which mimics anaerobic condition in the presence of oxygen. Uptake assays with radio- and fluorescently-labeled cholesterol revealed that 17 of the 33 mutants strongly affect uptake and/or esterification of exogenously supplied cholesterol. Examination of the subcellular distribution of sterols in these uptake mutants by cell fractionation and fluorescence microscopy indicates that some of the mutants block incorporation of cholesterol into the plasma membrane, a presumably early step in sterol uptake. Unexpectedly, the largest class of uptake mutants is affected in mitochondrial functions, and many of the uptake mutants show electron-dense mitochondrial inclusions. These results indicate that a hitherto uncharacterized mitochondrial function is required for sterol uptake and/or transport under anaerobic conditions and will be discussed in light of the fact that mitochondrial import of cholesterol is required for steroidogenesis in vertebrate cells.
These authors contributed equally to this work.
Address correspondence to:
Roger Schneiter (roger.schneiter{at}unifr.ch)
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