The transcription factors ADR1 or CAT8 are required for RTG pathway activation and evasion from yeast acetic acid-induced programmed cell death in raffinose
Authors:Luna Laera1,#, Nicoletta Guaragnella1,#, Maša Ždralević1,¶, Domenico Marzulli1, Zhengchang Liu2 and Sergio Giannattasio1
doi: 10.15698/mic2016.12.549
Volume 3, pp. 621 to 631, published 02/12/2016.
1 National Research Council of Italy, Institute of Biomembranes and Bioenergetics, Bari, Italy.
2 Department of Biological Sciences, University of New Orleans, New Orleans, LA, USA.
# L. L. and N. G. contributed equally to this work.
¶ Present address: Institute for Research on Cancer and Aging, CNRS-UMR 7284-INSERM U1081, University of Nice Sophia-Antipolis, Nice, France.
Keywords:
yeast, programmed cell death, mitochondrial retrograde pathway, glucose, carbon catabolite repression, acetic acid.
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflict of interest.
Please cite this article as:
Luna Laera, Nicoletta Guaragnella, Maša Ždralević, Domenico Marzulli, Zhengchang Liu and Sergio Giannattasio (2016). 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 3(12): 621-631. doi: 10.15698/mic2016.12.549
© 2016 Laera et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
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.