Adaptive capacity to dietary Vitamin B12 levels is maintained by a gene-diet interaction that ensures optimal life span.

Diet regulates complex life-history traits such as longevity. For optimal lifespan, organisms employ intricate adaptive mechanisms whose molecular underpinnings are less known. We show that Caenorhabditis elegans FLR-4 kinase prevents lifespan differentials on the bacterial diet having higher Vitamin B12 levels. The flr-4 mutants are more responsive to the higher B12 levels of Escherichia coli HT115 diet, and consequently, have enhanced flux through the one-carbon cycle. Mechanistically, a higher level of B12 transcriptionally downregulates the phosphoethanolamine methyltransferase pmt-2 gene, which modulates phosphatidylcholine (PC) levels. Pmt-2 downregulation activates cytoprotective gene expression through the p38-MAPK pathway, leading to increased lifespan only in the mutant. Evidently, preventing bacterial B12 uptake or inhibiting one-carbon metabolism reverses all the above phenotypes. Conversely, supplementation of B12 to E. coli OP50 or genetically reducing PC levels in the OP50-fed mutant extends lifespan. Together, we reveal how worms maintain adaptive capacity to diets having varying micronutrient content to ensure a normal lifespan.

Photocatalytic TiO2/CdS/ZnS nanocomposite induces Bacillus subtilis cell death by disrupting its metabolism and membrane integrity.

Titanium dioxide (TiO2) is widely characterized for its application in clinical diagnostics, therapeutics, cosmetics, nutrition, and environment management. Despite enormous potential, its dependence on ultraviolet (UV) light for photocatalytic activity limits its commercialization. Accordingly in the present study, a photo catalytically superior ternary complex of TiO2 with Cadmium sulfide/Zinc sulfide (CdS/ZnS) has been synthesized, as well as, characterized for photo-induced antimicrobial activity. The band gap of crystalline TiO2/CdS/ZnS nanocomposite has been reduced (2.26 eV) and nanocomposite has shown the optimal photo-activation at 590 nm. TiO2 nanocomposite has significant bactericidal activity in visible light (P < 0.01). Exposure of the TiO2 nanocomposite affected the cellular metabolism by altering the 1681 metabolic features (P < 0.001) culminating in poor cellular survivability. Additionally, photo-induced reactive oxygen species generation through nanocomposite disrupts the microbial cellular structure. The present study synthesized photocatalytic nanocomposite as well as unveiled the holistic cellular effect of theTiO2/CdS/ZnS nanocomposite. Additionally, the present study also indicated the potential application of TiO2/CdS/ZnS nanocomposite for sustainable environment management, therapeutics, and various industries. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-021-00973-z.

Ncl1-mediated metabolic rewiring critical during metabolic stress.

Nutritional limitation has been vastly studied; however, there is limited knowledge of how cells maintain homeostasis in excess nutrients. In this study, using yeast as a model system, we show that some amino acids are toxic at higher concentrations. With cysteine as a physiologically relevant example, we delineated the pathways/processes that are altered and those that are involved in survival in the presence of elevated levels of this amino acid. Using proteomics and metabolomics approach, we found that cysteine up-regulates proteins involved in amino acid metabolism, alters amino acid levels, and inhibits protein translation-events that are rescued by leucine supplementation. Through a comprehensive genetic screen, we show that leucine-mediated effect depends on a transfer RNA methyltransferase (NCL1), absence of which decouples transcription and translation in the cell, inhibits the conversion of leucine to ketoisocaproate, and leads to tricarboxylic acid cycle block. We therefore propose a role of NCL1 in regulating metabolic homeostasis through translational control.