1. PLoS One. 2009 Jun 16;4(6):e5942.

Genetic manipulation of palmitoylethanolamide production and inactivation in
Saccharomyces cerevisiae.

Muccioli GG, Sia A, Muchowski PJ, Stella N.

Department of Pharmacology, University of Washington, Seattle, Washington, United
States of America.

BACKGROUND: Lipids can act as signaling molecules, activating intracellular and
membrane-associated receptors to regulate physiological functions. To understand 
how a newly discovered signaling lipid functions, it is necessary to identify and
characterize the enzymes involved in their production and inactivation. The
signaling lipid N-palmitoylethanolamine (PEA) is known to activate intracellular 
and membrane-associated receptors and regulate physiological functions, but
little is known about the enzymes involved in its production and inactivation.
PRINCIPAL FINDINGS: Here we show that Saccharomyces cerevisiae produce and
inactivate PEA, suggesting that genetic manipulations of this lower eukaryote may
be used to identify the enzymes involved in PEA metabolism. Accordingly, using
single gene deletion mutants, we identified yeast genes that control PEA
metabolism, including SPO14 (a yeast homologue of the mammalian phospholipase D) 
that controls PEA production and YJU3 (a yeast homologue of the mammalian
monoacylglycerol lipase) that controls PEA inactivation. We also found that PEA
metabolism is affected by heterologous expression of two mammalian proteins
involved in neurodegenerative diseases, namely huntingtin and alpha-synuclein.
SIGNIFICANCE: Together these findings show that forward and reverse genetics in
S. cerevisiae can be used to identify proteins involved in PEA production and
inactivation, and suggest that mutated proteins causing neurodegenerative
diseases might affect the metabolism of this important signaling lipid.

PMCID: 2691958
PMID: 19529773 [PubMed - indexed for MEDLINE]