RRC ID 21927
Author Carvalho M, Schwudke D, Sampaio JL, Palm W, Riezman I, Dey G, Gupta GD, Mayor S, Riezman H, Shevchenko A, Kurzchalia TV, Eaton S.
Title Survival strategies of a sterol auxotroph.
Journal Development
Abstract The high sterol concentration in eukaryotic cell membranes is thought to influence membrane properties such as permeability, fluidity and microdomain formation. Drosophila cannot synthesize sterols, but do require them for development. Does this simply reflect a requirement for sterols in steroid hormone biosynthesis, or is bulk membrane sterol also essential in Drosophila? If the latter is true, how do they survive fluctuations in sterol availability and maintain membrane homeostasis? Here, we show that Drosophila require both bulk membrane sterol and steroid hormones in order to complete adult development. When sterol availability is restricted, Drosophila larvae modulate their growth to maintain membrane sterol levels within tight limits. When dietary sterol drops below a minimal threshold, larvae arrest growth and development in a reversible manner. Strikingly, membrane sterol levels in arrested larvae are dramatically reduced (dropping sixfold on average) in most tissues except the nervous system. Thus, sterols are dispensable for maintaining the basic membrane biophysical properties required for cell viability; these functions can be performed by non-sterol lipids when sterols are unavailable. However, bulk membrane sterol is likely to have essential functions in specific tissues during development. In tissues in which sterol levels drop, the overall level of sphingolipids increases and the proportion of different sphingolipid variants is altered. These changes allow survival, but not growth, when membrane sterol levels are low. This relationship between sterols and sphingolipids could be an ancient and conserved principle of membrane homeostasis.
Volume 137(21)
Pages 3675-85
Published 2010-11-1
DOI 10.1242/dev.044560
PII 137/21/3675
PMID 20940226
PMC PMC2964098
MeSH Animals Animals, Genetically Modified Cell Membrane / metabolism Cell Survival Cells, Cultured Drosophila / embryology Drosophila / growth & development* Drosophila / metabolism* Drosophila / physiology Embryo, Nonmammalian Hormones / metabolism Larva / growth & development Larva / metabolism Models, Biological Sphingolipids / metabolism Steroids / metabolism Sterols / metabolism* Survival / physiology
IF 5.611
Times Cited 64
Drosophila 30502R-1 30502R-4