Comparison of the transcriptomic "stress response" evoked by antimycin A and oxygen deprivation in saccharomyces cerevisiae

Abstract

BackgroundAcute changes in environmental parameters (e.g., O2, pH, UV, osmolarity, nutrients, etc.) evoke a common transcriptomic response in yeast referred to as the "environmental stress response" (ESR) or "common environmental response" (CER). Why such a diverse array of insults should elicit a common transcriptional response remains enigmatic. Previous functional analyses of the networks involved have found that, in addition to up-regulating those for mitigating the specific stressor, the majority appear to be involved in balancing energetic supply and demand and modulating progression through the cell cycle. Here we compared functional and regulatory aspects of the stress responses elicited by the acute inhibition of respiration with antimycin A and oxygen deprivation under catabolite non-repressed (galactose) conditions.ResultsGene network analyses of the transcriptomic responses revealed both treatments result in the transient (10 – 60 min) down-regulation of MBF- and SBF-regulated networks involved in the G1/S transition of the cell cycle as well as Fhl1 and PAC/RRPE-associated networks involved in energetically costly programs of ribosomal biogenesis and protein synthesis. Simultaneously, Msn2/4 networks involved in hexose import/dissimilation, reserve energy regulation, and autophagy were transiently up-regulated. Interestingly, when cells were treated with antimycin A well before experiencing anaerobiosis these networks subsequently failed to respond to oxygen deprivation. These results suggest the transient stress response is elicited by the acute inhibition of respiration and, we postulate, changes in cellular energetics and/or the instantaneous growth rate, not oxygen deprivation per se. After a considerable delay (≥ 1 generation) under anoxia, predictable changes in heme-regulated gene networks (e.g., Hap1, Hap2/3/4/5, Mot3, Rox1 and Upc2) were observed both in the presence and absence of antimycin A.ConclusionThis study not only differentiates between the gene networks that respond to respiratory inhibition and those that respond to oxygen deprivation but suggests the function of the ESR or CER is to balance energetic supply/demand and coordinate growth with the cell cycle, whether in response to perturbations that disrupt catabolic pathways or those that require rapidly up-regulating energetically costly programs for combating specific stressors.

Transcriptional Responses ofSaccharomyces cerevisiaeto Shift from Respiratory and Respirofermentative to Fully Fermentative Metabolism

“…The stress response in galactose-grown cells has been suggested to arise from cessation of respiration, which is less significant on glucose because respiratory activity is already low under glucose repression (Lai et al, 2005). In accordance with this hypothesis, it was recently shown that exposure of galactose-grown cells to antimycin A, an inhibitor of the respiratory chain, leads to a similar transient transcriptomic response as anoxia (Lai et al, 2008). On galactose and glycerol (Dirmeier et al, 2002;Guzy et al, 2007), but not on glucose (Guzy et al, 2007), exposure to anaerobic conditions also leads to a transient oxidative stress response.…”

Plant Core Environmental Stress Response Genes Are Systemically Coordinated during Abiotic Stresses

“…Studies in yeast have uncovered general stress responses, which were shown to activate similar sets of genes by various stresses [29–31]. These sets of genes are known as common environmental response (CER) in Saccharomyces cerevisiae [32] or core environmental stress response (CESR) in Schizosaccharomyces pombe [33].…”

Time-Course Analysis of Gene Expression During theSaccharomyces cerevisiaeHypoxic Response

“…Each of these secondary effects acts as a stimulus, activating a unique signaling pathway that regulates gene expression; heme depletion signals to the Hap1 pathway (Hickman and Winston 2007) while sterol depletion activates the Upc2/Ecm22 pathway (Hickman et al 2011). Furthermore, it has been suggested that some of the gene expression changes during hypoxia are due to a transient stress response (Lai et al 2008). Approximately 900 genes in the yeast genome respond to diverse types of stress and have been deemed part of the ESR (Gasch et al 2000).…”