Journal article
Evidence for the Bifunctional Nature of Mitochondrial Phosphatidylserine Decarboxylase: Role in Pdr3-Dependent Retrograde Regulation of PDR5 Expression
Molecular and cellular biology, Vol.28(19), pp.5851-5864
10/2008
DOI: 10.1128/MCB.00405-08
PMCID: PMC2547020
PMID: 18644857
Abstract
ABSTRACT
Multidrug resistance in the yeast
Saccharomyces cerevisiae
is sensitive to the mitochondrial genome status of cells. Cells that lose their organellar genome ([
rho
0
] cells) dramatically induce transcription of multiple or pleiotropic drug resistance genes via increased expression of a zinc cluster-containing transcription factor designated Pdr3. A major Pdr3 target gene is the ATP-binding cassette transporter-encoding gene
PDR5
. Pdr5 has been demonstrated to act as a phospholipid floppase catalyzing the net outward movement of phosphatidylethanolamine (PE). Since the mitochondrially localized Psd1 enzyme provides a major route of PE biosynthesis, we evaluated the potential linkage between Psd1 function and
PDR5
regulation. Overproduction of Psd1 in wild-type ([
rho
+
]) cells was found to induce
PDR5
transcription and drug resistance in a Pdr3-dependent manner. Loss of the
PSD1
gene from [
rho
0
] cells prevented the normal activation of
PDR5
expression. Surprisingly, expression of a catalytically inactive form of Psd1 still supported
PDR5
transcriptional activation, suggesting that PE levels were not the signal triggering
PDR5
induction. Expression of green fluorescent protein fusions mapped the region required to induce
PDR5
expression to the noncatalytic amino-terminal portion of Psd1. Psd1 is a novel bifunctional protein required both for PE biosynthesis and regulation of multidrug resistance.
Details
- Title: Subtitle
- Evidence for the Bifunctional Nature of Mitochondrial Phosphatidylserine Decarboxylase: Role in Pdr3-Dependent Retrograde Regulation of PDR5 Expression
- Creators
- Kailash Gulshan - University of IowaJennifer A. Schmidt - University of IowaPuja Shahi - University of IowaW. Scott Moye-Rowley - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biology, Vol.28(19), pp.5851-5864
- DOI
- 10.1128/MCB.00405-08
- PMID
- 18644857
- PMCID
- PMC2547020
- ISSN
- 0270-7306
- eISSN
- 1098-5549
- Language
- English
- Date published
- 10/2008
- Academic Unit
- Molecular Physiology and Biophysics; Internal Medicine
- Record Identifier
- 9984297598802771
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