SPHINGOLIPID FUNCTIONS INSACCHAROMYCES CEREVISIAE: Comparison to Mammals

Abstract

Many roles for sphingolipids have been identified in mammals. Available data suggest that sphingolipids and their intermediates also have diverse roles in Saccharomyces cerevisiae. These roles include signal transduction during the heat stress response, regulation of calcium homeostasis or components in calciummediated signaling pathways, regulation of the cell cycle, and functions as components in trafficking of secretory vesicles from the endoplasmic reticulum to the Golgi apparatus and as the lipid moiety in many glycosylphosphatidylinositolanchored proteins. S. cerevisiae is likely to be the first organism in which all genes involved in sphingolipid metabolism are identified. This information will provide an unprecedented opportunity to determine, for the first time in any organism, how sphingolipid synthesis is regulated. Through the use of both genetic and biochemical techniques, the identification of the complete array of processes regulated by sphingolipid signals is likely to be possible, as is the quantification of the physiological contribution of each. CONTENTS

Stress signals for apoptosis: ceramide and c-Jun kinase

“…Ceramide synthase has not yet been characterized at the molecular level and its activity has been detected only in endoplasmic reticulum and mitochondria (Hirschberg et al, 1993;Shimeno et al, 1995). A variant of this mechanism exists in yeast, where phytosphingosine is the predominant sphingoid base used for ceramide synthesis and the oxidation step is omitted (Dickson, 1998).…”

A new class of lipid desaturase central to sphingolipid biosynthesis and signalling

“…Sphingolipids are ubiquitous and essential components of the eukaryotic cell, but until recently these lipids were considered to play a purely biophysical role in cellular homeostasis [1]. The structure of sphingolipids can be considered analogous to phospholipids, comprising two acyl chains linked to a polar headgroup, although the actual composition of the two classes of lipids is different.…”

“…This LCB is synthesized by the condensation of saturated C [16][17][18] fatty acyl CoA with serine, followed by reduction, to yield the sphingoid LCB dihydrosphingosine. This LCB is then acylated to a long chain or very long chain fatty acid esterified to acyl-CoA to yield dihydroceramide, which then, in turn, serves as a substrate for further modifications to generate sphingolipids (primarily by the addition of a polar head group) [1].…”

“…The recent paper from Ernst Heinz's group in Hamburg, Germany, reports the identification of the ∆ 4 -LCB desaturasethis is a major breakthrough in our understanding of sphingolipid metabolism [1,7]. Using a bioinformatic approach, Philipp Ternes et al identified several hundred putative desaturases from several organisms, based on the presence of a catalytically essential motif known as the histidine box [8].…”

“…An insight into the role of this enzyme is now emerging from the recent analysis by Cláudio Gomes et al [1] who propose that alternative oxidases are evolutionarily related to other di-iron proteins and that an early function of these proteins was to scavenge di-oxygen. However, Lee Hansen et al [2] suggest that the present-day function of this enzyme is to allow flexible control of ATP synthesis to maintain growth rate homeostasis.…”