Acylspermidines are conserved mitochondrial sirtuin-dependent metabolites.

Sirtuins are nicotinamide adenine dinucleotide (NAD)-dependent protein lysine deacylases regulating metabolism and stress responses; however, characterization of the removed acyl groups and their downstream metabolic fates remains incomplete. Here we employed untargeted comparative metabolomics to reinvestigate mitochondrial sirtuin biochemistry. First, we identified N-glutarylspermidines as metabolites downstream of the mitochondrial sirtuin SIR-2.

Broad anti-pathogen potential of DEAD box RNA helicase eIF4A-targeting rocaglates.

Inhibition of eukaryotic initiation factor 4A has been proposed as a strategy to fight pathogens. Rocaglates exhibit the highest specificities among eIF4A inhibitors, but their anti-pathogenic potential has not been comprehensively assessed across eukaryotes. In silico analysis of the substitution patterns of six eIF4A1 aa residues critical to rocaglate binding, uncovered 35 variants.

Combinatorial Assembly of Modular Glucosides via Carboxylesterases Regulates Starvation Survival.

The recently discovered dular ucosides (MOGLs) form a large metabolite library derived from combinatorial assembly of moieties from amino acid, neurotransmitter, and lipid metabolism in the model organism . Combining CRISPR-Cas9 genome editing, comparative metabolomics, and synthesis, we show that the carboxylesterase homologue Cel-CEST-1.2 is responsible for specific 2--acylation of diverse glucose scaffolds with a wide variety of building blocks, resulting in more than 150 different MOGLs.

An excreted small molecule promotes C. elegans reproductive development and aging.

Excreted small-molecule signals can bias developmental trajectories and physiology in diverse animal species. However, the chemical identity of these signals remains largely obscure. Here we report identification of an unusual N-acylated glutamine derivative, nacq#1, that accelerates reproductive development and shortens lifespan in Caenorhabditis elegans.

Larval crowding accelerates C. elegans development and reduces lifespan.

Environmental conditions experienced during animal development are thought to have sustained impact on maturation and adult lifespan. Here we show that in the model organism C. elegans developmental rate and adult lifespan depend on larval population density, and that this effect is mediated by excreted small molecules.

Identifying evolutionarily conserved genes in the dietary restriction response using bioinformatics and subsequent testing in Caenorhabditis elegans.

Dietary restriction (DR) increases life span, health span and resistance to stress in a wide range of organisms. Work from a large number of laboratories has revealed evolutionarily conserved mechanisms that mediate the DR response. Here, we analyzed the genome-wide gene expression profiles of Caenorhabditis elegans under DR versus ad libitum conditions.

Pheromone sensing regulates Caenorhabditis elegans lifespan and stress resistance via the deacetylase SIR-2.1.

Lifespan in Caenorhabditis elegans, Drosophila, and mice is regulated by conserved signaling networks, including the insulin/insulin-like growth factor 1 (IGF-1) signaling cascade and pathways depending on sirtuins, a family of NAD(+)-dependent deacetylases. Small molecules such as resveratrol are of great interest because they increase lifespan in many species in a sirtuin-dependent manner. However, no endogenous small molecules that regulate lifespan via sirtuins have been identified, and the mechanisms underlying sirtuin-dependent longevity are not well understood.

Ascaroside signaling in C. elegans.

Over the past 10 years, the relevance of small-molecule signaling for many aspects of C. elegans development and behavior has become apparent. One prominent group of small-molecule signals are the ascarosides, which control dauer entry and exit as well as a variety of sex-specific and social behaviors, including male attraction, hermaphrodite repulsion, olfactory plasticity, and aggregation.

Ortho2ExpressMatrix--a web server that interprets cross-species gene expression data by gene family information.

Background: The study of gene families is pivotal for the understanding of gene evolution across different organisms and such phylogenetic background is often used to infer biochemical functions of genes. Modern high-throughput experiments offer the possibility to analyze the entire transcriptome of an organism; however, it is often difficult to deduct functional information from that data.

Results: To improve functional interpretation of gene expression we introduce Ortho2ExpressMatrix, a novel tool that integrates complex gene family information, computed from sequence similarity, with comparative gene expression profiles of two pre-selected biological objects: gene families are displayed with two-dimensional matrices.

Identification of a novel human Acyl-CoA binding protein isoform with a unique C-terminal domain.

Seven isoforms of the multifunctional human Acyl-coenzyme A binding protein (ACBP) have been characterized so far. Through ab initio analysis of expressed sequence tag (ESTs), we identified a novel high-abundant ACBP splice variant ACBP1e encoding an ACBP isoform with a unique C-terminus of 81 amino acid residues. Bioinformatic analysis shows that this domain is evolutionary conserved and shares no significant homology with other known proteins, and its function is not known.

A shortcut to identifying small molecule signals that regulate behavior and development in Caenorhabditis elegans.

Small molecule metabolites play important roles in Caenorhabditis elegans biology, but effective approaches for identifying their chemical structures are lacking. Recent studies revealed that a family of glycosides, the ascarosides, differentially regulate C. elegans development and behavior.

A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease.

Analysis of protein-protein interactions (PPIs) is a valuable approach for characterizing proteins of unknown function. Here, we have developed a strategy combining library and matrix yeast two-hybrid screens to generate a highly connected PPI network for Huntington's disease (HD). The network contains 186 PPIs among 35 bait and 51 prey proteins.

A novel nuclear receptor/coregulator complex controls C. elegans lipid metabolism, larval development, and aging.

Environmental cues transduced by an endocrine network converge on Caenorhabditis elegans nuclear receptor DAF-12 to mediate arrest at dauer diapause or continuous larval development. In adults, DAF-12 selects long-lived or short-lived modes. How these organismal choices are molecularly specified is unknown.