Investigation of the effects of apoptosis, autophagy and retrograde transcription on the expression of CYC1, SUC2 and GPD1 genes

Apoptosis is a programmed cell death mechanism that allows the cell to eliminate itself in physiological and pathological conditions. Autophagy, which can be triggered by starvation or other stimuli, is the recycling of damaged organelles and misfolded proteins in a double membrane structure called an autophagosome. Retrograde control is the signaling pathway from the mitochondrion to the nucleus that is activated by mitochondrial damages and Krebs cycle disturbances. Upon activation by retrograde signaling, certain transcription factors enter the nucleus and activate the transcription of mitochondrial genes resulting in the repair of mitochondrial damages. In S. cerevisiae, GPD1, CYC1, and SUC2 genes encode glycerol-3-phosphate dehydrogenase enzyme, cytochrome-c isoform-1 protein, and invertase enzyme, respectively. In this study, the effects of apoptosis, autophagy and retrograde control on the transcription of GPD1, CYC1, and SUC2 genes were investigated. Activation of apoptosis conditions resulted in the transcriptional repression of GPD1, CYC1, and SUC2 genes. In autophagy conditions, while GPD1 gene transcription decreased at low levels in wild yeast strain, CYC1 gene transcription was not affected. Transcription of SUC2 repressed by 3-fold in autophagy induced conditions. It was observed that Hog1p and Tor1p kinases had different effects on the transcription of these genes under apoptosis and autophagy conditions. Our results also indicated that apoptosis conditions completely prevent invertase secretion. However, autophagy activation did not have severe effects on invertase secretion the yeast cells. The Rtg1/3p complex, which is the transcription factor of the retrograde control mechanism, binds to the sequence called R box in the promoters of the retrograde targeted genes. The promoter regions of the GPD1, CYC1, and SUC2 genes were analyzed for R box sequences using bioinformatics tools, and multiple R-boxes were identified within the promoter regions of those genes. Altogether, these results indicate that transcription of GPD1, CYC1, and SUC2 genes, which have significant metabolic functions in cells, are controlled at certain levels depending on autophagy, apoptosis, and retrograde signaling.