Exposure of Saccharomyces cerevisiae to acetaldehyde induces sulfur amino acid metabolism and polyamine transporter genes, which depend on Met4p and Haa1p transcription factors, respectively

Abstract

Acetaldehyde is a toxic compound produced by Saccharomyces cerevisiae cells under several growth conditions. The adverse effects of this molecule are important, as significant amounts accumulate inside the cells. By means of global gene expression analyses, we have detected the effects of acetaldehyde addition in the expression of about 400 genes. Repressed genes include many genes involved in cell cycle control, cell polarity, and the mitochondrial protein biosynthesis machinery. Increased expression is displayed in many stress response genes, as well as other families of genes, such as those encoding vitamin B1 biosynthesis machinery and proteins for aryl alcohol metabolism. The induction of genes involved in sulfur metabolism is dependent on Met4p and other well-known factors involved in the transcription of MET genes under nonrepressing conditions of sulfur metabolism. Moreover, the deletion of MET4 leads to increased acetaldehyde sensitivity. TPO genes encoding polyamine transporters are also induced by acetaldehyde; in this case, the regulation is dependent on the Haa1p transcription factor. In this paper, we discuss the connections between acetaldehyde and the processes affected by this compound in yeast cells with reference to the microarray data.

FIG. 1.

Distribution of acetaldehyde-induced and -repressed genes into the most representative functional categories according to the Fatigo algorithm.

FIG. 2.

Transcriptional regulation of TPO genes by acetaldehyde. The blots show hybridization (with specific probes corresponding to the genes indicated) of RNA samples from exponentially growing cells in 2% (wt/vol) glucose (YPD medium; samples 0) and 1 h after incubation in the presence of 1 g of acetaldehyde/liter (samples A). The ACT1 gene was used as a loading control. Experiments were performed at least twice. The figure shows the results of one representative experiment.

FIG. 3.

Scheme of the steps of the sulfate assimilation pathway affected by the presence of acetaldehyde, according to microarray analysis results. APS, 5′-adenylylsulfate; PAPS, 3′-phospho-5′-adenylylsulfate.

FIG. 4.

Transcriptional regulation of sulfur metabolism genes by acetaldehyde. (A) Effect of mutants in several transcription factors (mainly involved in the regulation of sulfur metabolism genes) on the expression of several genes induced by acetaldehyde. The blots show hybridization (with specific probes corresponding to the genes indicated) of RNA samples from exponentially growing cells in 2% (wt/vol) glucose (YPD medium; samples 0) and 1 h after incubation in the presence of 1 g of acetaldehyde/liter (samples A). The ACT1 gene was used as a loading control. Experiments were performed at least twice. The figure shows the results of one representative experiment. (B) Effect of methionine level in the growth medium on the expression of several acetaldehyde-induced genes. Experiments were performed as described for panel A, but cells were grown in SD medium with or without 1 mM methionine. WT, wild type.

FIG. 5.

Effect of mutations in several sulfur metabolism genes on resistance to acetaldehyde. Five-microliter aliquots of serial dilutions from exponential cultures in YPD medium (2% [wt/vol] glucose) were spotted onto YPD or YPD plus acetaldehyde (1 g/liter) plates. Plates were incubated for several days until colonies appeared. Experiments were performed at least three times. The figure shows the results of one representative experiment.