Multiple signals from dysfunctional mitochondria activate the pleiotropic drug resistance pathway in Saccharomyces cerevisiae

Timothy C Hallstrom; W Scott Moye-Rowley

doi:10.1074/jbc.M007338200

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Multiple signals from dysfunctional mitochondria activate the pleiotropic drug resistance pathway in Saccharomyces cerevisiae

Journal article

Open access

Peer reviewed

Multiple signals from dysfunctional mitochondria activate the pleiotropic drug resistance pathway in Saccharomyces cerevisiae

Timothy C Hallstrom and W Scott Moye-Rowley

The Journal of biological chemistry, Vol.275(48), pp.37347-37356

12/01/2000

DOI: 10.1074/jbc.M007338200

PMID: 10980204

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Abstract

Multiple or pleiotropic drug resistance most often occurs in Saccharomyces cerevisiae due to substitution mutations within the Cys(6)-Zn(II) transcription factors Pdr1p and Pdr3p. These dominant transcriptional regulatory proteins cause elevated drug resistance and overexpression of the ATP-binding cassette transporter-encoding gene, PDR5. We have carried out a genetic screen to identify negative regulators of PDR5 expression and found that loss of the mitochondrial genome (rho(o) cells) causes up-regulation of Pdr3p but not Pdr1p function. Additionally, loss of the mitochondrial inner membrane protein Oxa1p generates a signal that results in increased Pdr3p activity. Both of these mitochondrial defects lead to increased expression of the PDR3 structural gene. Importantly, the signaling pathway used to enhance Pdr3p function in rho(o) cells is not the same as in oxa1 cells. Loss of previously described nuclear-mitochondrial signaling genes like RTG1 reduce the level of PDR5 expression and drug resistance seen in rho(o) cells but has no effect on oxa1-induced phenotypes. These data uncover a new regulatory pathway connecting expression of multidrug resistance genes with mitochondrial function.

Signal Transduction

ATP-Binding Cassette Transporters - genetics

Base Sequence

DNA Primers

Drug Resistance, Microbial - genetics

Genes, Fungal

Membrane Proteins - genetics

Mitochondria - metabolism

Saccharomyces cerevisiae - genetics

Saccharomyces cerevisiae - metabolism

Saccharomyces cerevisiae Proteins

Details

Title: Subtitle: Multiple signals from dysfunctional mitochondria activate the pleiotropic drug resistance pathway in Saccharomyces cerevisiae
Creators: Timothy C Hallstrom - University of Iowa
W Scott Moye-Rowley - University of Iowa
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.275(48), pp.37347-37356
DOI: 10.1074/jbc.M007338200
PMID: 10980204
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Grant note: GM49825 / NIGMS NIH HHS
Language: English
Date published: 12/01/2000
Academic Unit: Molecular Physiology and Biophysics; Internal Medicine
Record Identifier: 9984297609102771

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