PARP catalysed ADP-ribosylation is a post-translational modification involved in several physiological and pathological processes, including cellular stress. In order to visualise both Poly-, and Mono-, ADP-ribosylation in vivo, we engineered specific fluorescent probes. Using them, we show that amino-acid starvation triggers an unprecedented display of mono-ADP-ribosylation that governs the formation of Sec body, a recently identified stress assembly that forms in Drosophila cells. We show that dPARP16 catalytic activity is necessary and sufficient for both amino-acid starvation induced mono-ADP-ribosylation and subsequent Sec body formation and cell survival. Importantly, dPARP16 catalyses the modification of Sec16, a key Sec body component, and we show that it is a critical event for the formation of this stress assembly. Taken together our findings establish a novel example for the role of mono-ADP-ribosylation in the formation of stress assemblies, and link this modification to a metabolic stress.
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http://dx.doi.org/10.7554/eLife.21475 | DOI Listing |
J Mol Neurosci
December 2024
Department of Neurosurgery, National Children's Medical Center (Shanghai), Children's Hospital of Fudan University, No.399 Wan Yuan Avenue, Minhang District, Shanghai, 201102, China.
Focal cortical dysplasia (FCD) II is a cortical malformation characterized by cortical architectural abnormalities, dysmorphic neurons, with or without balloon cells. Here, we systematically explored the pathophysiological role of the GATOR1 subunit NPRL3 variants including a novel mutation from iPSCs derived from one FCD II patient. Three FCD II children aged 0.
View Article and Find Full Text PDFmBio
December 2024
Department of Microbiology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Bacteria encounter numerous stressors in their constantly changing environments and have evolved many methods to deal with stressors quickly and effectively. One well-known and broadly conserved stress response in bacteria is the stringent response, mediated by the alarmone (p)ppGpp. (p)ppGpp is produced in response to amino acid starvation and other nutrient limitations and stresses and regulates both the activity of proteins and expression of genes.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, USA. Electronic address:
Glutathione (GSH) is an abundant thiol-containing tripeptide that functions in redox homeostasis, protein folding, and iron metabolism. In Saccharomyces cerevisiae, GSH depletion leads to increased sensitivity to oxidants and other toxic compounds, disruption of Fe-S cluster biogenesis, and eventually cell death. GSH pools are supplied by intracellular biosynthesis and GSH import from the extracellular environment.
View Article and Find Full Text PDFmSystems
December 2024
Department of Bioengineering, University of California, San Diego, California, USA.
Unlabelled: The composition of bacterial transcriptomes is determined by the transcriptional regulatory network (TRN). The TRN regulates the transition from one physiological state to another. Here, we use independent component analysis to monitor the composition of the transcriptome during the transition from the exponential growth phase to the stationary phase.
View Article and Find Full Text PDFA 60-year-old polymorbid patient developed severe metabolic acidosis during weeks of treatment with flucloxacillin and paracetamol. The acidosis was triggered by an accumulation of 5-oxoproline due to pre-existing risk factors for glutathione deficiency as well as a ketoacidosis due to starvation. After treatment with N-acetylcysteine and hemofiltration, the acidosis completely resolved.
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