Intracellular pH and Lipid Metabolism: Intracellular pH regulates metabolism by poorly understood mechanisms, but biosensors are likely to be important in this process. Young et al. (p. 1085 ) took a systems-biology approach in yeast to identify in excess of 200 genes that regulate phospholipid metabolism. They found that the signaling lipid, phosphatidic acid, appeared to act as a cytosolic biosensor via the pH-dependent binding of protein effectors to phosphatidic acid. This pH-dependent mechanism directly affects gene expression and is involved in a pathway in which nutrient availability regulates phospholipid metabolism to control production of membranes.

Sterols and sphingolipids are limited to eukaryotic cells, and their interaction has been proposed to favor formation of lipid microdomains. Although there is abundant biophysical evidence demonstrating their interaction in simple systems, convincing evidence is lacking to show that they function together in cells. Using lipid analysis by mass spectrometry and a genetic approach on mutants in sterol metabolism, we show that cells adjust their membrane composition in response to mutant sterol structures preferentially by changing their sphingolipid composition. Systematic combination of mutations in sterol biosynthesis with mutants in sphingolipid hydroxylation and head group turnover give a large number of synthetic and suppression phenotypes. Our unbiased approach provides compelling evidence that sterols and sphingolipids function together in cells. We were not able to correlate any cellular phenotype we measured with plasma membrane fluidity as measured using fluorescence anisotropy. This questions whether the increase in liquid order phases that can be induced by sterol–sphingolipid interactions plays an important role in cells. Our data revealing that cells have a mechanism to sense the quality of their membrane sterol composition has led us to suggest that proteins might recognize sterol–sphingolipid complexes and to hypothesize the coevolution of sterols and sphingolipids.

MicrobeMASST, a taxonomically informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbe-derived metabolites and relative producers without a priori knowledge will vastly enhance the understanding of microorganisms’ role in ecology and human health.

Recent rapid growth of lipidomics is mainly attributed to technological advances in mass spectrometry. Development of soft ionization techniques, in combination with computational tools, has spurred subsequent development of various methods for lipid analysis. However, none of these existing approaches can cover major cellular lipids in a single run. Here we demonstrate that a single method of liquid chromatography coupled with mass spectrometry (LCMS) can be used for simultaneous profiling of major cellular lipids including glycerophospholipids (PLs), sphingolipids (SPLs), waxes, sterols (ST) and mono-, di- as well as triacylglycerides (MAG, DAG, TAG). We applied this approach to analyze these lipids in various organisms including Saccharomyces cerevisiae and Schizosaccharomyces pombe. While phospholipids and triacylglycerides of S. pombe mainly contain 18 : 1 fatty acyls, those of S. cerevisiae contain 16 : 1, 16 : 0 and 18 : 1 fatty acyls. S. cerevisiae and S. pombe contain distinct sphingolipid profiles. S. cerevisiae has abundant inositol phytoceramides (IPC), while S. pombe contains high levels of free phytoceramides as well as short chain phytoceramides (t18:1/20 : 0-B) and IPC (t18:1/20 : 0-B). In S. cerevisiae, our results demonstrated accumulation of ergosterol esters in tgl1Δ cells and accumulation of various TAG species in tgl3Δ cells, which are consistent with the function of the respective enzymes. Furthermore, we, for the first time, systematically characterized lipids in S. pombe and measured their dynamic changes in Δplh1Δdga1 cells at different growth phases. We further discussed dynamic changes of phospholipids, sphingolipids and neutral lipids in the progress of programmed cell death in Δplh1Δdga1 cells of S. pombe.