title: The transcription factorsADR1orCAT8are required for RTG pathway activation and evasion from yeast acetic acid-induced programmed cell death in raffinose.
abstract: YeastSaccharomyces cerevisiaegrown 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 asCIT2, encoding peroxisomal citrate synthase, dependent on the positive regulatorRTG2in 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 lackingRTG2and/or certain factors regulating carbon source utilization, includingMIG1,HXK2,ADR1,CAT8, andHAP4, have been analyzed for their survival andCIT2expression after acetic acid treatment.ADR1andCAT8were identified as positive regulators ofRTG-dependent gene transcription.ADR1andCAT8interact withRTG2and with each other in inducing cell resistance to AA-PCD in raffinose and controlling the nature of cell death. In the absence ofADR1andCAT8, AA-PCD evasion is acquired through activation of an alternative factor/pathway repressed byRTG2,suggesting thatRTG2may 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 andSNF1-dependent relief of CCR have a key role in central carbon metabolism reprogramming which modulates the yeast acetic acid-stress response.
authors.affiliation: National Research Council of Italy, Institute of Biomembranes and Bioenergetics, Bari, Italy.
authors.forename: Luna
authors.initials: L
authors.lastname: Laera
authors.affiliation: National Research Council of Italy, Institute of Biomembranes and Bioenergetics, Bari, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Guaragnella
authors.affiliation: National Research Council of Italy, Institute of Biomembranes and Bioenergetics, Bari, Italy.
authors.forename: Maša
authors.initials: M
authors.lastname: Ždralević
authors.affiliation: National Research Council of Italy, Institute of Biomembranes and Bioenergetics, Bari, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Marzulli
authors.affiliation: Department of Biological Sciences, University of New Orleans, New Orleans, LA, USA.
authors.forename: Zhengchang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: National Research Council of Italy, Institute of Biomembranes and Bioenergetics, Bari, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Giannattasio
keywords: acetic acid; carbon catabolite repression; glucose; mitochondrial retrograde pathway; programmed cell death; yeast