The transcription factors ADR1 or CAT8 are required for RTG pathway activation and evasion from yeast acetic acid-induced programmed cell death in raffinose

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-...

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Main Authors: Luna Laera, Nicoletta Guaragnella, Maša Ždralević, Domenico Marzulli, Zhengchang Liu, Sergio Giannattasio
Format: Article
Language:English
Published: Shared Science Publishers OG 2016-12-01
Series:Microbial Cell
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Online Access:http://microbialcell.com/researcharticles/the-transcription-factors-adr1-or-cat8-are-required-for-rtg-pathway-activation-and-evasion-from-yeast-acetic-acid-induced-programmed-cell-death-in-raffinose/
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author Luna Laera
Nicoletta Guaragnella
Maša Ždralević
Domenico Marzulli
Zhengchang Liu
Sergio Giannattasio
author_facet Luna Laera
Nicoletta Guaragnella
Maša Ždralević
Domenico Marzulli
Zhengchang Liu
Sergio Giannattasio
author_sort Luna Laera
collection DOAJ
description 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 of RTG-dependent gene transcription. ADR1 and CAT8 interact with RTG2 and with each other in inducing cell resistance to AA-PCD in raffinose and controlling the nature of cell death. In the absence of ADR1 and CAT8, AA-PCD evasion is acquired through activation of an alternative factor/pathway repressed by RTG2, suggesting that RTG2 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 SNF1-dependent relief of CCR have a key role in central carbon metabolism reprogramming which modulates the yeast acetic acid-stress response.
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spelling doaj-art-d2af0e97388d48c6949f780580ca97502025-08-20T02:52:37ZengShared Science Publishers OGMicrobial Cell2311-26382016-12-0131262163110.15698/mic2016.12.549The transcription factors ADR1 or CAT8 are required for RTG pathway activation and evasion from yeast acetic acid-induced programmed cell death in raffinoseLuna Laera0Nicoletta Guaragnella1Maša Ždralević2Domenico Marzulli3Zhengchang LiuSergio Giannattasio4National Research Council of Italy, Institute of Biomembranes and Bioenergetics, Bari, Italy.National Research Council of Italy, Institute of Biomembranes and Bioenergetics, Bari, Italy.National Research Council of Italy, Institute of Biomembranes and Bioenergetics, Bari, Italy.National Research Council of Italy, Institute of Biomembranes and Bioenergetics, Bari, Italy.National Research Council of Italy, Institute of Biomembranes and Bioenergetics, Bari, Italy.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 of RTG-dependent gene transcription. ADR1 and CAT8 interact with RTG2 and with each other in inducing cell resistance to AA-PCD in raffinose and controlling the nature of cell death. In the absence of ADR1 and CAT8, AA-PCD evasion is acquired through activation of an alternative factor/pathway repressed by RTG2, suggesting that RTG2 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 SNF1-dependent relief of CCR have a key role in central carbon metabolism reprogramming which modulates the yeast acetic acid-stress response.http://microbialcell.com/researcharticles/the-transcription-factors-adr1-or-cat8-are-required-for-rtg-pathway-activation-and-evasion-from-yeast-acetic-acid-induced-programmed-cell-death-in-raffinose/yeastprogrammed cell deathmitochondrial retrograde pathwayglucosecarbon catabolite repressionacetic acid
spellingShingle Luna Laera
Nicoletta Guaragnella
Maša Ždralević
Domenico Marzulli
Zhengchang Liu
Sergio Giannattasio
The transcription factors ADR1 or CAT8 are required for RTG pathway activation and evasion from yeast acetic acid-induced programmed cell death in raffinose
Microbial Cell
yeast
programmed cell death
mitochondrial retrograde pathway
glucose
carbon catabolite repression
acetic acid
title The transcription factors ADR1 or CAT8 are required for RTG pathway activation and evasion from yeast acetic acid-induced programmed cell death in raffinose
title_full The transcription factors ADR1 or CAT8 are required for RTG pathway activation and evasion from yeast acetic acid-induced programmed cell death in raffinose
title_fullStr The transcription factors ADR1 or CAT8 are required for RTG pathway activation and evasion from yeast acetic acid-induced programmed cell death in raffinose
title_full_unstemmed The transcription factors ADR1 or CAT8 are required for RTG pathway activation and evasion from yeast acetic acid-induced programmed cell death in raffinose
title_short The transcription factors ADR1 or CAT8 are required for RTG pathway activation and evasion from yeast acetic acid-induced programmed cell death in raffinose
title_sort transcription factors adr1 or cat8 are required for rtg pathway activation and evasion from yeast acetic acid induced programmed cell death in raffinose
topic yeast
programmed cell death
mitochondrial retrograde pathway
glucose
carbon catabolite repression
acetic acid
url http://microbialcell.com/researcharticles/the-transcription-factors-adr1-or-cat8-are-required-for-rtg-pathway-activation-and-evasion-from-yeast-acetic-acid-induced-programmed-cell-death-in-raffinose/
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