Interorganellar Communication: ALTERED NUCLEAR GENE EXPRESSION PROFILES IN A YEAST MITOCHONDRIAL DNA MUTANT

Ana Traven,Johnson M.S Wong,Deming Xu,Mary Sopta,C James Ingles

doi:10.1074/jbc.m006807200

Abstract

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.

Highlights

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
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
Exhaustion of glucose leads to a transient growth arrest called the diauxic transition, whereupon cells induce transcription of nuclear genes coding for proteins of the mitochondrial transcriptional and translational apparatus and for components of the respiratory complexes as they adapt to respiratory metabolism [9]

Summary

Introduction

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. 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. Glucose represses respiratory activity and mitochondrial biosynthesis irrespective of whether oxygen is present This transcriptional regulation by oxygen and glucose of nucleus-encoded proteins related to mitochondrial functions is mediated via regulation of the activity of the Hap and Hap2/3/4/5 activator proteins, respectively [7], which together regulate the expression of genes encoding components of the electron transport complexes as well as genes coding for enzymes of the tricarboxylic acid cycle and the heme, sterol, and fatty acid biosynthetic pathways [2]. It has been suggested that low activity of the cAMP-PKA pathway facilitates mitochondrial biogenesis [23,24,25]

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Conclusion