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Molecular and Cellular Biology, October 2008, p. 5851-5864, Vol. 28, No. 19
0270-7306/08/$08.00+0     doi:10.1128/MCB.00405-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Evidence for the Bifunctional Nature of Mitochondrial Phosphatidylserine Decarboxylase: Role in Pdr3-Dependent Retrograde Regulation of PDR5 Expression{triangledown}

Kailash Gulshan, Jennifer A. Schmidt, Puja Shahi, and W. Scott Moye-Rowley*

Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242

Received 10 March 2008/ Returned for modification 14 April 2008/ Accepted 15 July 2008

Multidrug resistance in the yeast Saccharomyces cerevisiae is sensitive to the mitochondrial genome status of cells. Cells that lose their organellar genome ([rho0] 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 [rho0] 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.

* Corresponding author. Mailing address: Department of Molecular Physiology and Biophysics, 6-530 Bowen Science Building, 51 Newton Road, Iowa City, IA 52242. Phone: (319) 335-8774. Fax: (319) 335-7330. E-mail: scott-moye-rowley{at}uiowa.edu

{triangledown} Published ahead of print on 21 July 2008.

Molecular and Cellular Biology, October 2008, p. 5851-5864, Vol. 28, No. 19
0270-7306/08/$08.00+0     doi:10.1128/MCB.00405-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Osman, C., Haag, M., Potting, C., Rodenfels, J., Dip, P. V., Wieland, F. T., Brugger, B., Westermann, B., Langer, T. (2009). The genetic interactome of prohibitins: coordinated control of cardiolipin and phosphatidylethanolamine by conserved regulators in mitochondria. JCB 184: 583-596 [Abstract] [Full Text]  


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