The transcription factors ADR1 orCAT8 are required for RTG pathway activation and evasionfrom yeast acetic acid-induced programmed cell death inraffinose

摘要

Yeast Saccharomyces cerevisiae grown on glucose undergoes programmed cell death (PCD) induced by acetic acid (AA-PCD), but evades PCD when grown in raffinose. This is due to concomitant relief of carbon catabolite repression (CCR) and activation of mitochondrial retrograde signaling, a mitochondria-to-nucleus communication pathway causing up-regulation of various nuclear target genes, such as CIT2, encoding peroxisomal citrate synthase, dependent on the positive regulator RTG2 in response to mitochondrial dysfunction. CCR down-regulates genes mainly involved in mitochondrial respiratory metabolism. In this work, we investigated the relationships between the RTG and CCR pathways in the modulation of AA-PCD sensitivity under glucose repression or de-repression conditions. Yeast single and double mutants lacking RTG2 and/or certain factors regulating carbon source utilization, including MIG1, HXK2, ADR1, CAT8, and HAP4, have been analyzed for their survival and CIT2 expression after acetic acid treatment. ADR1 and CAT8 were identified as positive regulators ofRTG-dependent gene transcription. ADR1 andCAT8 interact with RTG2 and with eachother in inducing cell resistance to AA-PCD in raffinose and controlling thenature of cell death. In the absence of ADR1 andCAT8, AA-PCD evasion is acquired through activation of analternative factor/pathway repressed by RTG2, suggestingthat RTG2 may play a function in promoting necrotic celldeath in repressing conditions when RTG pathway is inactive. Moreover, our datashow that simultaneous mitochondrial retrograde pathway activation andSNF1-dependent relief of CCR have a key role in centralcarbon metabolism reprogramming which modulates the yeast acetic acid-stressresponse.