Reference: Alvarez-Vasquez F, et al. (2011) Mathematical modeling and validation of the ergosterol pathway in Saccharomyces cerevisiae. PLoS One 6(12):e28344

Reference Help

Abstract


The de novo biosynthetic machinery for both sphingolipid and ergosterol production in yeast is localized in the endoplasmic reticulum (ER) and Golgi. The interconnections between the two pathways are still poorly understood, but they may be connected in specialized membrane domains, and specific knockouts strongly suggest that both routes have different layers of mutual control and are co-affected by drugs. With the goal of shedding light on the functional integration of the yeast sphingolipid-ergosterol (SL-E) pathway, we constructed a dynamic model of the ergosterol pathway using the guidelines of Biochemical Systems Theory (BST) (Savageau., J. theor. Biol., 25, 365-9, 1969). The resulting model was merged with a previous mathematical model of sphingolipid metabolism in yeast (Alvarez-Vasquez et al., J. theor. Biol., 226, 265-91, 2004; Alvarez-Vasquez et al., Nature433, 425-30, 2005). The S-system format within BST was used for analyses of consistency, stability, and sensitivity of the SL-E model, while the GMA format was used for dynamic simulations and predictions. Model validation was accomplished by comparing predictions from the model with published results on sterol and sterol-ester dynamics in yeast. The validated model was used to predict the metabolomic dynamics of the SL-E pathway after drug treatment. Specifically, we simulated the action of drugs affecting sphingolipids in the endoplasmic reticulum and studied changes in ergosterol associated with microdomains of the plasma membrane (PM).

Reference Type
Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't | Research Support, U.S. Gov't, Non-P.H.S.
Authors
Alvarez-Vasquez F, Riezman H, Hannun YA, Voit EO
Primary Lit For
Additional Lit For
Review For

Gene Ontology Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene/Complex Qualifier Gene Ontology Term Aspect Annotation Extension Evidence Method Source Assigned On Reference

Phenotype Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Disease Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Disease Ontology Term Qualifier Evidence Method Source Assigned On Reference

Regulation Annotations


Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, SPELL, or YeastMine.

Regulator Target Direction Regulation Of Happens During Method Evidence

Post-translational Modifications


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Site Modification Modifier Reference

Interaction Annotations


Genetic Interactions

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Assay Annotation Action Modification Source Reference

Functional Complementation Annotations


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Species Gene ID Strain background Direction Details Source Reference