Research ResourceLipid Signaling

Distinct Signaling Roles of Ceramide Species in Yeast Revealed Through Systematic Perturbation and Systems Biology Analyses

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Sci. Signal.  29 Oct 2013:
Vol. 6, Issue 299, pp. rs14
DOI: 10.1126/scisignal.2004515

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Unraveling Ceramide Signaling Specificity

The extensive biochemical complexity of the ceramide class of lipids, with more than 30 species in yeast and hundreds in mammals, creates challenges for discerning the specific functions of individual species of ceramide or subgroups of these lipids. Montefusco et al. took a systems biology approach to tackle the functional complexity of ceramide-regulated events in yeast using a biosynthetic inhibitor to limit the number of species produced. The authors clustered changes in lipid abundance with functionally related transcriptional changes in yeast subjected to heat stress to identify changes in gene expression that correlated with specific classes of ceramides. Mapping of the lipid-correlated transcriptional profiles to transcription factors identified putative transcriptional modules regulated by changes in ceramide abundance, and two of these modules were experimentally verified in yeast. Thus, this approach and the data set will help unravel specificity in ceramide-mediated regulatory events.