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Originally published In Press as doi:10.1074/jbc.M006807200 on October 27, 2000

J. Biol. Chem., Vol. 276, Issue 6, 4020-4027, February 9, 2001
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Interorganellar Communication
ALTERED NUCLEAR GENE EXPRESSION PROFILES IN A YEAST MITOCHONDRIAL DNA MUTANT*

Ana TravenDagger §, Johnson M. S. Wong§, Deming Xu§, Mary SoptaDagger , and C. James Ingles§||**

From the Dagger  Department of Molecular Genetics, Institute Rudjer Boskovic, Bijenicka 54, 10000 Zagreb, Croatia and § Banting and Best Department of Medical Research and || Department of Molecular and Medical Genetics, University of Toronto, Ontario M5G 1L6, Canada

Communication between mitochondria and the nucleus is important for a variety of cellular processes such as carbohydrate and nitrogen metabolism, mating and sporulation, and cell growth and morphogenesis. It has long been known that the functional state of mitochondria can influence nuclear gene expression. For example, in yeast cells lacking the mitochondrial genome, the expression of several nuclear genes, such as CIT2 (citrate synthase), MRP13 (mitochondrial ribosomal protein), and DLD3 (D-lactate dehydrogenase) has been reported to be altered. Here we show by microarray analysis of the genome-wide transcription profile of Saccharomyces cerevisiae that yeast petite mutants lacking mitochondrial DNA induce genes coding for mitochondrial proteins, enzymes of the glycolytic pathway and of the citric acid cycle, cell wall components, membrane transporters, and genes normally induced by nutrient deprivation and a variety of stresses. Consistent with the observed induction of genes related to cell stress and those encoding membrane transporters, yeast petite cells showed increased resistance to severe heat shock and exhibited a pleiotropic drug resistance phenotype. The observed changes in nuclear gene expression in cells lacking mitochondrial DNA may have implications for the role of mitochondria in processes such as carcinogenesis and aging.

* This work was supported by a grant from the Medical Research Council (MRC) of Canada (to C. J. I.) and from the Croatian Ministry of Science and Technology (to M. S.). The Microarray Centre at the Ontario Cancer Institute is supported by funding from the MRC of Canada, the National Research Council of Canada, and the National Science and Engineering Research Council of Canada.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Recipient of a graduate scholarship from the Croatian Ministry of Science and Technology.

** To whom correspondence should be addressed: Banting and Best Dept. of Medical Research, University of Toronto, 112 College St., Toronto, Ontario M5G 1L6, Canada. Tel.: 416-978-7400; Fax: 416-978-8528; E-mail: cj.ingles@utoronto.ca.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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