The role of transcriptional ‘futile cycles’ in autophagy and microbial pathogenesis

Hu, Guowu; McQuiston, Travis; Bernard, Amélie; Park, Yoon-Dong; Qiu, Jin; Vural, Ali; Zhang, Nannan; Waterman, Scott R.; Blewett, Nathan H.; Myers, Timothy G.; Kehrl, John H.; Uzel, Gülbû; Klionsky, Daniel J.; Williamson, Peter R.

doi:10.15698/mic2015.08.221

Cited by 3 publications

(2 citation statements)

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“…Compared to the published large-scale genome studies, our data show that the Spt4-Spt5 complex may act in a gene-specific manner in budding yeast, with Spt4 having an additional and clear negative role for certain ATG genes under growing conditions. This type of regulation fits with the observation that stress-response genes, such as ATG genes are regulated in a manner that is opposite to most genes encoding proteins that function during vegetative growth [36,37]. The deletion of SPT4 leads to an increase of ATG8/Atg8 and ATG41/Atg41, and the change in ATG41 expression in particular facilitates an increase in autophagy activity.…”

Section: Discussionsupporting

confidence: 82%

The transcription factor Spt4-Spt5 complex regulates the expression of ATG8 and ATG41

et al. 2019

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Macroautophagy/autophagy, a highly conserved dynamic process, is one of the major degradative pathways in cells. So far, over 40 autophagy-related (ATG) genes have been identified in Saccharomyces cerevisiae, most of which have homologs in more complex eukaryotes. Autophagy plays a crucial role in cell survival and maintenance, and its dysfunction is related to various diseases, indicating that the proper regulation of autophagy is important. Although the overall process of autophagy has been extensively studied, in particular with regard to the function of the Atg proteins, relatively little is known about the regulatory mechanisms that control autophagy activity. Spt5 is one of the transcriptional factors that is universally conserved across all domains. This protein can form a complex with Spt4, together playing a central role in transcription. In complex eukaryotic cells, the Spt4-Spt5 complex plays a dual role in gene regulation, acting both to delay transcription through promoter-proximal pausing, and to facilitate transcriptional elongation. In contrast, in S. cerevisiae, only the positive function of the Spt4-Spt5 complex has been identified. Here, we show for the first time that the Spt4-Spt5 transcription factor complex negatively regulates ATG genes in S. cerevisiae, inhibiting autophagy activity during active growth. Under autophagy-inducing conditions, the repression is released by Spt5 phosphorylation, allowing an upregulation of autophagy activity.

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Section: Discussionsupporting

confidence: 82%

The transcription factor Spt4-Spt5 complex regulates the expression of ATG8 and ATG41

et al. 2019

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“…For surviving, the cells have to draw on the other interconnected metabolites to compensate for this carbohydrate deprivation. Gluconeogenesis is a typical way to replenish the carbohydrates and is sensitive to glucose deficiency [115]. Up regulation of gluconeogenesis could transiently refuel the cells while consuming precursor metabolites derived from other metabolism and finally resulting in the comprehensive starvation of the cells.…”

Section: Discussionmentioning

confidence: 99%

Cuminal Inhibits Trichothecium roseum Growth by Triggering Cell Starvation: Transcriptome and Proteome Analysis

Zhang

et al. 2020

Microorganisms

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Trichothecium roseum is a harmful postharvest fungus causing serious damage, together with the secretion of insidious mycotoxins, on apples, melons, and other important fruits. Cuminal, a predominant component of Cuminum cyminum essential oil has proven to successfully inhibit the growth of T. roseum in vitro and in vivo. Electron microscopic observations revealed cuminal exposure impaired the fungal morphology and ultrastructure, particularly the plasmalemma. Transcriptome and proteome analysis was used to investigate the responses of T. roseum to exposure of cuminal. In total, 2825 differentially expressed transcripts (1516 up and 1309 down) and 225 differentially expressed proteins (90 up and 135 down) were determined. Overall, notable parts of these differentially expressed genes functionally belong to subcellular localities of the membrane system and cytosol, along with ribosomes, mitochondria and peroxisomes. According to the localization analysis and the biological annotation of these genes, carbohydrate and lipids metabolism, redox homeostasis, and asexual reproduction were among the most enriched gene ontology (GO) terms. Biological pathway enrichment analysis showed that lipids and amino acid degradation, ATP-binding cassette transporters, membrane reconstitution, mRNA surveillance pathway and peroxisome were elevated, whereas secondary metabolite biosynthesis, cell cycle, and glycolysis/gluconeogenesis were down regulated. Further integrated omics analysis showed that cuminal exposure first impaired the polarity of the cytoplasmic membrane and then triggered the reconstitution and dysfunction of fungal plasmalemma, resulting in handicapped nutrient procurement of the cells. Consequently, fungal cells showed starvation stress with limited carbohydrate metabolism, resulting a metabolic shift to catabolism of the cell's own components in response to the stress. Additionally, these predicaments brought about oxidative stress, which, in collaboration with the starvation, damaged certain critical organelles such as mitochondria. Such degeneration, accompanied by energy deficiency, suppressed the biosynthesis of essential proteins and inhibited fungal growth.fungicides to be used for postharvest treatment, reduced efficacy due to the emergence of pathogen resistance to these chemicals, and the growing public concerns over chemical residues in food and the environment have necessitated the seeking of alternative solutions to control the fungal spoilage and to guarantee food safety and consumer health [8].Essential oils (EOs), generally recognized as safe by the US Food and Drug Administration [9], are natural substances with established antimicrobial activities [10,11] and are a candidate instrument for controlling postharvest disease [12,13]. Nonetheless, this candidacy is compromised by the expensiveness of these natural substances due to their generally low yields. However, exploring their mode of actions is valuable to the development of novel alternatives.The multicomponent EOs attribute their mode of act...

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Investigation of the Inhibitory Effects of Illicium verum Essential Oil Nanoemulsion on Fusarium proliferatum via Combined Transcriptomics and Metabolomics Analysis

Ling,

Liao,

Wen

et al. 2024

Curr Microbiol

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The role of transcriptional ‘futile cycles’ in autophagy and microbial pathogenesis

Cited by 3 publications

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The transcription factor Spt4-Spt5 complex regulates the expression of ATG8 and ATG41

The transcription factor Spt4-Spt5 complex regulates the expression of ATG8 and ATG41

Cuminal Inhibits Trichothecium roseum Growth by Triggering Cell Starvation: Transcriptome and Proteome Analysis

Investigation of the Inhibitory Effects of Illicium verum Essential Oil Nanoemulsion on Fusarium proliferatum via Combined Transcriptomics and Metabolomics Analysis

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