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Molecular Regulation of Lipid Metabolism

Principal Investigator: Dr. Virginia McDonough

Microorganisms maintain growth and reproduction by utilizing nutrients in their environment for energy. My research interests center on the exploration of the regulation of lipid metabolism, using the model eukaryote Saccharomyces cerevisiae. My research tests the hypothesis that specific genetic mutations will prevent S. cerevisiae from sensing and utilizing lipids in their environment. In recent work, we have isolated
mutants in S. cerevisiae that exhibit increased growth sensitivity to a mildly toxic fatty acid, and appear deficient in the metabolism and cellular response to exogenous fatty acids. Characterization of the mutants has identified several gene products and pathways that are involved in response to exogenous fatty acids, including MGA2 and PDR16. These two gene products are not directly concerned with fatty acid uptake, but seem to be
involved in cellular response to fatty acid supplementation. We have found that cells harboring a mutation in pdr16 are not only growth defective on medium chain fatty acids, but also contain elevated amounts of sterols and fatty acids, have an altered fatty acid composition, and are deficient in the esterification of fed fatty acids. Mutants mga2 expression results in some, but not all, of the same defects. Using both molecular
genetic and biochemical approaches, we are currently investigating the precise roles of the PDR16- and MGA2- encoded proteins in regulating lipid metabolism and traffic, and the interaction/overlap between these separate pathways. Students in my laboratory assist with hypothesis formation, experimental design, and data acquisition and analysis. Students also routinely read and discuss scientific literature and develop skills for writing and presenting their data.

Representative Publications:

  • Iverson, S.*, Sonnemann, K.*, Reddick, A.*, McDonough, V. 2006 Expression of the S. cerevisiae PIS1 gene is modulated by multiple ATGs in the promoter. Biochem Biophys Res Commun. 350(1):91-6
  • Forés, O., Arró, M., Pahissa, A., Ferrero, S., Germann, M., Stukey, J. , McDonough, V., Nickels, J.T. Jr., Campos, N., Ferrer, 2006 A. Arabidopsis thaliana expresses two functional isoforms of Arvp, a protein involved in the regulation of cellular lipid homeostasis. Biochim. Biophys. Acta, 1761(7):725-35
  • Germann M, Gallo C, Donahue T, Shirzadi R, Stukey J, Lang S, Ruckenstuhl C, Oliaro-Bosso S, McDonough V, Turnowsky F, Balliano G, Nickels JT Jr. 2005 Characterizing sterol defect suppressors uncovers a novel transcriptional signaling pathway regulating zymosterol biosynthesis. J Biol Chem. 280(43):35904-13
  • McDonough, V.M., Roth T.* 2004 Growth temperature affects accumulation of exogenous fatty acids and fatty acid composition in Schizosaccharomyces pombe. Antonie van Leeuwenhoek. 86:349-354
  • McDonough, V.M., Stukey, J., Cavanagh, T.* 2002 Mutations in erg4 affect the sensitivity of Saccharomyces cerevisiae to medium chain fatty acids. Biochim. Biophys. Acta. 1581 (3) pp. 109-118
  • Swain E., Baudry K., Stukey J., McDonough V., Germann M., Nickels JT Jr. 2002 Sterol-dependent Regulation of Sphingolipid Metabolism in Saccharomyces cerevisiae. J. Biol. Chem. 277(29):26177-84
  • Swain E, Stukey J, McDonough V, Germann M, Liu Y., Sturley S., Nickels JT Jr. 2002 Yeast Cells Lacking the ARV1 Gene Harbor Defects in Sphingolipid Metabolism: Complementation by Human hARV1. J. Biol Chem. 277(39):36152-60

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