Conventional and emerging roles of the energy sensor Snf1/AMPK in Saccharomyces cerevisiae

Coccetti, Paola; Nicastro, Raffaele; Tripodi, Farida

doi:10.15698/mic2018.11.655

Cited by 71 publications

(75 citation statements)

References 151 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In both of our replicates, Snf1 T210 is dephosphorylated at the G1/S transition and re-phosphorylated as cells progress into mitosis consistent with the hypothesis that changing phosphatase activity may drive large-scale dephosphorylation through G1/S. The dephosphorylation of Snf1 through G1/S may be important because when Snf1 is activated (like AMPK in mammals) it acts as a "brake pedal" slowing growth and energy consuming processes (Ghillebert et al, 2011;Coccetti et al, 2018). Thus, Snf1 inactivates many processes typically activated by PKA (Nicastro et al, 2015).…”

Section: Discussionsupporting

confidence: 81%

Multiple Layers of Phospho-Regulation Coordinate Metabolism and the Cell Cycle in Budding Yeast

Zhang

Winkler

Schlottmann

et al. 2019

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 81%

Multiple Layers of Phospho-Regulation Coordinate Metabolism and the Cell Cycle in Budding Yeast

Zhang

Winkler

Schlottmann

et al. 2019

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Despite the essential role of SnRK1 in plant growth and stress response, the molecular mechanisms regulating SnRK1 complex function are largely unknown and only few substrates have been identified so far 11 . This is in contrast to 216 physical interactors identified for Snf1 in yeast 19 and over 60 targets identified through phosphorylation prediction and high-throughput studies for the mammalian AMPK 8,10 , pointing to a need for large scale identification of SnRK1 interactors in plants. Activation of SnRK1 or ABA treatment results in 20-30% overlapping transcriptional changes, suggesting these important stress pathways share common target genes 17 .…”

mentioning

confidence: 75%

An abscisic acid-responsive protein interaction network for sucrose non-fermenting related kinase1 in abiotic stress response

et al. 2020

View full text Add to dashboard Cite

Yeast Snf1 (Sucrose non-fermenting1), mammalian AMPK (5′ AMP-activated protein kinase) and plant SnRK1 (Snf1-Related Kinase1) are conserved heterotrimeric kinase complexes that re-establish energy homeostasis following stress. The hormone abscisic acid (ABA) plays a crucial role in plant stress response. Activation of SnRK1 or ABA signaling results in overlapping transcriptional changes, suggesting these stress pathways share common targets. To investigate how SnRK1 and ABA interact during stress response in Arabidopsis thaliana, we screened the SnRK1 complex by yeast two-hybrid against a library of proteins encoded by 258 ABA-regulated genes. Here, we identify 125 SnRK1-interacting proteins (SnIPs). Network analysis indicates that a subset of SnIPs form signaling modules in response to abiotic stress. Functional studies show the involvement of SnRK1 and select SnIPs in abiotic stress responses. This targeted study uncovers the largest set of SnRK1 interactors, which can be used to further characterize SnRK1 role in plant survival under stress.

show abstract

Section: Resultsmentioning

confidence: 99%

“…The AMP-activated protein kinase (AMPK) Snf1 plays an important role in energy homeostasis by acting as an ATP sensor that is activated by phosphorylation following energy depletion [52]. Activated Snf1 stimulates processes leading to the production of ATP and the shut-down of ATP-consuming processes [52]. In metazoans, hypoxia reduces ATP production by lowering the activity of the electron transport chain which led to the activation of the Snf1/AMPK protein kinase [1].…”

Section: Resultsmentioning

confidence: 99%

A novel genetic circuitry governing hypoxic metabolic flexibility, commensalism and virulence in the fungal pathogen Candida albicans

Burgain

Pic

Markey

et al. 2019

Preprint

View full text Add to dashboard Cite

Inside the human host, the pathogenic yeast Candida albicans colonizes predominantly oxygen-poor niches such as the gastrointestinal and vaginal tracts, but also oxygen-rich environments such as cutaneous epithelial cells and oral mucosa. This suppleness requires an effective mechanism to reprogram reversibly the primary metabolism in response to oxygen variation. Here, we have uncovered that Snf5, a subunit of SWI/SNF chromatin remodeling complex, is a major transcriptional regulator that links oxygen status to the metabolic capacity of C. albicans. Snf5 and other subunits of SWI/SNF complex were required to activate genes of alternative carbon utilization and other carbohydrates related process specifically under hypoxia. snf5 mutant exhibited an altered metabolome reflecting that SWI/SNF plays an essential role in maintaining metabolic homeostasis and carbon flux in C. albicans under hypoxia. Snf5 was necessary to activate the transcriptional program linked to both commensal and invasive growth. Accordingly, snf5 was unable to maintain its growth in the stomach, the cecum and the colon of mice. snf5 was also avirulent as it was unable to invade Galleria larvae or to cause damage to human enterocytes and murine macrophages. Among candidates of signaling pathways in which Snf5 might operate, phenotypic analysis revealed that mutants of Ras1-cAMP-PKA pathway, as well as mutants of Yak1 and Yck2 kinases exhibited a similar carbon flexibility phenotype as did snf5 under hypoxia. Genetic interaction analysis indicated that the adenylate cyclase Cyr1, a key component of the Ras1-cAMP pathway, but not Ras1, interacted genetically with Snf5. Our study yielded unprecedented insight into the oxygen-sensitive regulatory circuit that control metabolic flexibility, stress, commensalism and virulence in C. albicans.Author SummaryA critical aspect of eukaryotic cell fitness is the ability to sense and adapt to variations in oxygen concentrations in their local environment. Hypoxia leads to a substantial remodeling of cell metabolism and energy homeostasis, and thus, organisms must develop an effective regulatory mechanism to cope with oxygen depletion. Candida albicans is an opportunistic yeast that is the most prevalent human fungal pathogens. This yeast colonizes diverse niches inside the human host with contrasting carbon sources and oxygen concentrations. While hypoxia is the predominant conditions that C. albicans encounters inside most of the niches, the impact of this condition on metabolic flexibility, a major determinant of fungal virulence, was completely neglected. Here, we uncovered that the chromatin remodelling complex SWI/SNF is master regulatory circuit that links oxygen status to a broad spectrum of carbon utilization routes. Snf5 was essential for the maintenance of C. albicans as a commensal and also for the expression of its virulence. The oxygen-sensitive regulators identified in this work provide a framework to comprehensively understand the virulence of human fungal pathogens and represent a therapeutic value to fight fungal infections.

show abstract

Conventional and emerging roles of the energy sensor Snf1/AMPK in Saccharomyces cerevisiae

Cited by 71 publications

References 151 publications

Multiple Layers of Phospho-Regulation Coordinate Metabolism and the Cell Cycle in Budding Yeast

Multiple Layers of Phospho-Regulation Coordinate Metabolism and the Cell Cycle in Budding Yeast

An abscisic acid-responsive protein interaction network for sucrose non-fermenting related kinase1 in abiotic stress response

A novel genetic circuitry governing hypoxic metabolic flexibility, commensalism and virulence in the fungal pathogen Candida albicans

Contact Info

Product

Resources

About