Accumulation of squalene is associated with the clustering of lipid droplets

FEBS J. 2012 Nov;279(22):4231-44. doi: 10.1111/febs.12015. Epub 2012 Oct 22.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Animals
  • Antifungal Agents / pharmacology
  • CHO Cells
  • Cricetinae
  • Ergosterol / metabolism
  • Lipids / chemistry*
  • Mice
  • Naphthalenes / pharmacology
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Squalene / metabolism*
  • Squalene Monooxygenase / antagonists & inhibitors
  • Squalene Monooxygenase / metabolism*
  • Terbinafine

Substances

  • Antifungal Agents
  • Lipids
  • Naphthalenes
  • Squalene
  • Squalene Monooxygenase
  • Terbinafine
  • Ergosterol