Accumulation of squalene is associated with the clustering of lipid droplets

• Published in: The FEBS journal Vol. 279; no. 22; pp. 4231 - 4244
• Main Authors: Ta, Minh T., Kapterian, Tamar S., Fei, Weihua, Du, Ximing, Brown, Andrew J., Dawes, Ian W., Yang, Hongyuan
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.11.2012
• Subjects: 3T3-L1 Cells; Animals; Antifungal Agents - pharmacology; Biosynthesis; Cellular biology; CHO Cells; clustering; Cricetinae; erg1; Ergosterol - metabolism; lipid droplet; Lipids; Lipids - chemistry; Mice; Morphology; Naphthalenes - pharmacology; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae - metabolism; squalene; Squalene - metabolism; Squalene Monooxygenase - antagonists & inhibitors; Squalene Monooxygenase - metabolism; sterol biosynthesis
• ISSN: 1742-464X; 1742-4658; 1742-4658
• DOI: 10.1111/febs.12015

The isoprenoid squalene is an important precursor for the biosynthesis of sterols. The cellular storage of squalene and its impact on membrane properties have been the subject of recent investigations. In a screen for abnormal lipid droplet morphology and distribution in the yeast Saccharomyces cerevisiae, we found significant lipid droplet clustering (arbitrarily defined as an aggregation of six or more lipid droplets) in a number of mutants (e.g. erg1) that are defective in sterol biosynthesis. Interestingly, these mutants are also characterized by accumulation of large amounts of squalene. Reducing the level of squalene in these mutants restored normal lipid droplet distribution. Moreover, inhibition of squalene monooxygenase in two mammalian cell lines (CHO‐K1 and 3T3‐L1) by terbinafine also resulted in lipid droplet clustering. These results indicate that the level of squalene may affect the growth and distribution of lipid droplets. The biogenesis, growth and cellular distribution of lipid droplets are not well understood. Through genome‐wide screening in the budding yeast, we found extensive clustering of lipid droplets (arbitrarily defined as aggregation of six or more droplets) in cells that accumulate squalene due to reduced expression of ERG1. Additional experiments establish a link between squalene and the clustering of lipid droplets.