The Histidine Ammonia Lyase of Trypanosoma cruzi Is Involved in Acidocalcisome Alkalinization and Is Essential for Survival under Starvation Conditions

Trypanosoma cruzi is the etiologic agent of Chagas disease and is characterized by the presence of acidocalcisomes, organelles rich in phosphate and calcium. Release of these molecules, which are necessary for growth and cell signaling, is induced by alkalinization, but a physiological mechanism for acidocalcisome alkalinization was unknown. In this work, we demonstrate that a histidine ammonia lyase localizes to acidocalcisomes and is responsible for their alkalinization.

RIPK1 regulates starvation resistance by modulating aspartate catabolism

RIPK1 is a crucial regulator of cell death and survival. Ripk1 deficiency promotes mouse survival in the prenatal period while inhibits survival in the early postnatal period without a clear mechanism. Metabolism regulation and autophagy are critical to neonatal survival from severe starvation at birth. However, the mechanism by which RIPK1 regulates starvation resistance and survival remains unclear. Here, we address this question by discovering the metabolic regulatory role of RIPK1. First, metabolomics analysis reveals that Ripk1 deficiency specifically increases aspartate levels in both mouse neonates and mammalian cells under starvation conditions. Increased aspartate in Ripk1−/− cells enhances the TCA flux and ATP production. The energy imbalance causes defective autophagy induction by inhibiting the AMPK/ULK1 pathway. Transcriptional analyses demonstrate that Ripk1−/− deficiency downregulates gene expression in aspartate catabolism by inactivating SP1. To summarize, this study reveals that RIPK1 serves as a metabolic regulator responsible for starvation resistance.

Metabolome Characteristics of Liver Autophagy Deficiency under Starvation Conditions in Infancy

The liver function is essential for metabolism, detoxification, and bile synthesis, even in the neonatal period. Autophagy plays significance roles in THE adult liver, whereas the role of liver autophagy in the early neonatal period largely remains unclear. To clarify the importance of liver autophagy in the neonatal starvation period, we generated liver-specific autophagy-deficient (Atg5flox/flox; Albumin-Cre) mice and investigated under starvation conditions comparing with control (Atg5flox/+; Albumin-Cre) mice, focusing on serum metabolites and liver histopathology. As a result, autophagy in the liver was found to unessential for the survival under postnatal starvation. A metabolomics analysis of serum metabolites by gas chromatography-tandem mass spectrometry showed a significant difference between the groups, especially after 12-h starvation, suggesting the synergistical adaption of metabolic pathways, such as the “malate-aspartate shuttle”, “aspartate metabolism”, “urea cycle”, and “glycine and serine metabolism”. Liver-specific autophagy-deficiency under postnatal starvation conditions can cause a characteristic metabolic alteration suggesting a change of the mitochondrial function. Neonates seemed to maintain ketone production under starvation conditions, even in the autophagy-deficient liver, through a change in the mitochondrial function, which may be an adaptive mechanism for avoiding fatal starvation.

Insights into Transcriptional Regulation by Individual H3K4 Methylation Marks in S. Cerevisiae

Set1 is a lysine methyltransferase in S. cerevisiae that catalyzes the mono, di and tri methylation of the fourth lysine on the amino terminal tail of histone H3 (H3K4). Set1-like methyltransferases are evolutionarily conserved, and research has linked their function to developmental gene regulation and several cancers in higher eukaryotes. Set1 is a member of the multiprotein COMPASS complex in S. cerevisiae. The H3K4 methylation activity of COMPASS regulates gene expression and chromosome segregation in vivo. The three distinct methyl marks on histone H3K4 act in discrete ways to regulate transcription. Trimethylation of H3K4 is usually associated with active transcription whereas dimethylation of H3K4 is associated with gene repression. In this study, amino acid substitution mutants of SET1 that encode partial function Set1 proteins capable of H3K4me1, H3K4me1 and H3K4me2, or H3K4me1and H3K4me3 were analyzed to learn more about the roles of individual H3K4 methyl marks in transcription. The findings reveal a previously unappreciated role for H3K4me1 in activation of transcription of the HIS3 gene in S. cerevisiae cultures grown under histidine-starvation conditions. Surprisingly, induction of the HIS3 gene in cultures grown under histidine starvation is not accompanied by significant changes in the profiles of H3K4-methylated nucleosomes at the HIS3 gene in SET1 wild-type strains and set1 partial-function mutants. The data show that H3K4me1 supports induction of HIS3 mRNA to wild-type levels under histidine-starvation conditions and that higher-order H3K4 methylation (H3K4me2 and H3K4me3) is not required.

Comparative Transcriptome Analysis of Sophora japonica (L.) Roots Reveals Key Pathways and Genes in Response to PEG-Induced Drought Stress under Different Nitrogen Conditions

Sophora japonica is a native leguminous tree species in China. The high stress tolerance contributes to its long lifespan of thousands of years. The lack of genomic resources greatly limits genetic studies on the stress responses of S. japonica. In this study, RNA-seq was conducted for S. japonica roots grown under short-term 20% polyethylene glycol (PEG) 6000-induced drought stress under normal N and N starvation conditions (1 and 0 mM NH4NO3, respectively). In each of the libraries, we generated more than 25 million clean reads, which were then de novo assembled to 46,852 unigenes with an average length of 1310.49 bp. In the differential expression analyses, more differentially expressed genes (DEGs) were found under drought with N starvation than under single stresses. The number of transcripts identified under N starvation and drought in S. japonica was nearly the same, but more upregulated genes were induced by drought, while more downregulated genes were induced by N starvation. Genes involved in “phenylpropanoid biosynthesis” and “biosynthesis of amino acids” pathways were upregulated according to KEGG enrichment analyses, irrespective of the stress treatments. Additionally, upregulated N metabolism genes were enriched upon drought, and downregulated photosynthesis genes were enriched under N starvation. We found 4372 and 5430 drought-responsive DEGs under normal N and N starvation conditions, respectively. N starvation may aggravate drought by downregulating transcripts in the “carbon metabolism”, “ribosome”, “arginine biosynthesis pathway”, “oxidative phosphorylation” and “aminoacyl-tRNA biosynthesis” pathways. We identified 78 genes related to N uptake and assimilation, 38 of which exhibited differential expression under stress. A total of 395 DEGs were categorized as transcription factors, of which AR2/ERF-ERF, WRKY, NAC, MYB, bHLH, C3H and C2C2-Dof families played key roles in drought and N starvation stresses. The transcriptome data obtained, and the genes identified facilitate our understanding of the mechanisms of S. japonica responses to drought and N starvation stresses and provide a molecular foundation for understanding the mechanisms of its long lifespan for breeding resistant varieties for greening.

Glycolytically impaired glial cells fuel neural metabolism via β-oxidation

Neuronal function is highly energy demanding and thus requires efficient and constant metabolite delivery. Like their mammalian counterparts Drosophila glia are highly glycolytic and provide lactate to fuel neuronal metabolism. However, flies are able to survive for several weeks in the absence of glial glycolysis1. Here, we study how glial cells maintain sufficient nutrient supply to neurons under conditions of carbohydrate restriction. We show that glycolytically impaired glia switch to fatty acid breakdown via β-oxidation and provide ketone bodies as an alternate neuronal fuel. Moreover, flies also rely on glial β-oxidation under starvation conditions with glial loss of β-oxidation increasing susceptibility to starvation. Further, we show that glial cells act as a metabolic sensor in the brain and can induce mobilization of peripheral energy stores to ensure brain metabolic homeostasis. In summary, our study gives pioneering evidence on the importance of glial β-oxidation and ketogenesis for brain function, and survival, under adverse conditions, like malnutrition. The glial capacity to utilize lipids as an energy source seems to be conserved from flies to humans.

Characterization of glutathione S-transferase enzymes in Dictyostelium discoideum suggests a functional role for the GSTA2 isozyme in cell proliferation and development

In this report, we extend our previous characterization of Dictyostelium discoideum glutathione S-transferase (DdGST) enzymes that are expressed in the eukaryotic model organism. Transcript profiling of gstA1-gstA5 (alpha class) genes in vegetative, log phase cells identified gstA2 and gstA3 with highest expression (6–7.5-fold, respectively) when compared to other gstA transcripts. Marked reductions in all gstA transcripts occurred under starvation conditions, with gstA2 and gstA3 exhibiting the largest decreases (-96% and -86.6%, respectively). When compared to their pre-starvation levels, there was also a 60 percent reduction in total GST activity. Glutathione (GSH) pull-down assay and mass spectroscopy detected three isozymes (DdGSTA1, DdGSTA2 and DdGSTA3) that were predominantly expressed in vegetative cells. Biochemical and kinetic comparisons between rDdGSTA2 and rDdGSTA3 shows higher activity of rDdGSTA2 to the CDNB (1-chloro-2,4-dinitrobenzene) substrate. RNAi-mediated knockdown of endogenous DdGSTA2 caused a 60 percent reduction in proliferation, delayed development, and altered morphogenesis of fruiting bodies, whereas overexpression of rDdGSTA2 enzyme had no effect. These findings corroborate previous studies that implicate a role for phase II GST enzymes in cell proliferation, homeostasis, and development in eukaryotic cells.

Conclusion

The Red Army broke the back of the Wehrmacht, liberated Auschwitz and other camps, and freed millions from occupation. Its strength, however, was determined by civilians on the home front. The greatest victory of the twentieth century depended on their efforts. The Stalinist state reached the height of its powers during the war, manifesting a greater ability to mobilize its people than any other combatant nation. The evacuation and rebuilding of the industrial base, mass mobilization of workers, food allocation under starvation conditions, aversion of a public health disaster, and reconstruction of the liberated territories were the result of unprecedented organizational efforts. Strict discipline and repression played a role. Yet, without the support of the vast majority of people, the achievements on the home front would not have been possible. The war has now become central to a new Russian national identity. The victory of the Soviet people against fascism, however, is also part of an ongoing international struggle against virulent nationalism, race hatred, anti-Semitism, and exploitation.