Mitochondria are pivotal organelles that govern cellular energy production through the oxidative phosphorylation system utilizing five respiratory complexes. In addition, mitochondria also contribute to various critical signaling pathways including apoptosis, damage-associated molecular patterns, calcium homeostasis, lipid, and amino acid biosynthesis. Among these diverse functions, the energy
Extensive desmoplasia and poor vasculature renders pancreatic tumors severely hypoxic, contributing to their aggressiveness and therapy resistance. Here, we identify the HuR/MYB/HIF1a axis as a critical regulator of the metabolic plasticity and hypoxic survival of pancreatic cancer cells. HuR undergoes nuclear-to-cytoplasmic translocation under hypoxia and stabilizes MYB transcripts, while MYB transcriptionally upregulates HIF1a. Upon MYB silencing, pancreatic cancer cells fail to survive and adapt metabolically under hypoxia, despite forced overexpression of HIF1a. MYB induces the transcription of several HIF1a-regulated glycolytic genes by directly binding to their promoters, thus enhancing the recruitment of HIF1a to hypoxia-responsive elements through its interaction with p300-dependent histone acetylation. MYB-depleted pancreatic cancer cells exhibit a dramatic reduction in tumorigenic ability, glucose-uptake and metabolism in orthotopic mouse model, even after HIF1a restoration. Together, our findings reveal an essential role of MYB in metabolic reprogramming that supports pancreatic cancer cell survival under hypoxia.
A bacterial strain, designated ASS-1, was isolated and identified from a sediment sample of the river Ganges, Allahabad, India. The strain was Gram-stain-negative, formed straw-yellow pigmented colonies, was strictly aerobic, motile with a single polar flagellum, and positive for oxidase and catalase. The major fatty acids were C16 : 1ω7c/ 16 : 1 C16 : 1ω6c, C18 : 1ω7c and C16 : 0. Sequence analysis based on the 16S rRNA gene revealed that strain ASS-1 showed high similarity to Pseudomonas guguanensis CC-G9A (98.2 %), Pseudomonas alcaligenes ATCC 14909 (98.2 %), Pseudomonas oleovorans DSM 1045 (98.1 %), Pseudomonas indolxydans IPL-1 (98.1 %) and Pseudomonas toyotomiensis HT-3 (98.0 %). Analysis of its rpoB and rpoD housekeeping genes confirmed its phylogenetic affiliation and showed identities lower than 93 % with respect to the closest relatives. Phylogenetic analysis based on the 16S rRNA, rpoB, rpoD genes and the whole genome assigned it to the genus Pseudomonas. The results of digital DNA-DNA hybridization based on the genome-to-genome distance calculator and average nucleotide identity revealed low genome relatedness to its close phylogenetic neighbours (below the recommended thresholds of 70 and 95 %, respectively, for species delineation). Strain ASS-1 also differed from the related strains by some phenotypic characteristics, i.e. growth at pH 5.0 and 42 °C, starch and casein hydrolysis, and citrate utilization. Therefore, based on data obtained from phenotypic and genotypic analysis, it is evident that strain ASS-1 should be regarded as a novel species within the genus Pseudomonas, for which the name Pseudomonasfluvialis sp. nov. is proposed. The type strain is ASS-1 (=KCTC 52437=CCM 8778).
A Gram-stain-negative, rod-shaped, aerobic, straw yellow, motile strain, designated KNDSW-TSA6, belonging to the genus Acidovorax, was isolated from a water sample of the river Ganges, downstream of the city of Kanpur, Uttar Pradesh, India. Cells were aerobic, non-endospore-forming and motile with single polar flagella. It differed from its phylogenetically related strains by phenotypic characteristics such as hydrolysis of urea, gelatin, casein and DNA, and the catalase reaction. The major fatty acids were C16 : 1ω7c/C16 : 1ω6c, C16 : 0 and C18 : 1ω7c/C18 : 1ω6c. Phylogenetic analysis based on 16S rRNA and housekeeping genes (gyrb, recA and rpoB gene sequences), confirmed its placement within the genus Acidovorax as a novel species. Strain KNDSW-TSA6 showed highest 16S rRNA sequence similarity to Acidovorax soli BL21 (98.9 %), Acidovorax delafieldii ATCC 17505 (98.8 %), Acidovorax temperans CCUG 11779 (98.2 %), Acidovorax caeni R-24608 (97.9 %) and Acidovorax radicis N35 (97.6 %). The digital DNA-DNA hybridization and average nucleotide identity values calculated from whole genome sequences between strain KNDSW-TSA6 and the two most closely related strains A. soli BL21 and A. delafieldii ATCC 17505 were below the threshold values of 70 and 95 % respectively. Thus, the data from the polyphasic taxonomic analysis clearly indicates that strain KNDSW-TSA6 represents a novel species, for which the name Acidovorax kalamii sp. nov. is proposed. The type strain is Acidovorax kalamii (=MTCC 12652=KCTC 52819=VTCC-B-910010).
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