The transcription factors or are required for RTG pathway activation and evasion from yeast acetic acid-induced programmed cell death in raffinose.

Yeast 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 , encoding peroxisomal citrate synthase, dependent on the positive regulator 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 and/or certain factors regulating carbon source utilization, including , , , , and , have been analyzed for their survival and expression after acetic acid treatment. and were identified as positive regulators of -dependent gene transcription. and interact with and with each other in inducing cell resistance to AA-PCD in raffinose and controlling the nature of cell death. In the absence of and , AA-PCD evasion is acquired through activation of an alternative factor/pathway repressed by suggesting that may play a function in promoting necrotic cell death in repressing conditions when RTG pathway is inactive. Moreover, our data show that simultaneous mitochondrial retrograde pathway activation and -dependent relief of CCR have a key role in central carbon metabolism reprogramming which modulates the yeast acetic acid-stress response.