Lysosome-related organelles contain an expansion compartment that mediates delivery of zinc transporters to promote homeostasis.

Zinc is an essential nutrient-it is stored during periods of excess to promote detoxification and released during periods of deficiency to sustain function. Lysosome-related organelles (LROs) are an evolutionarily conserved site of zinc storage, but mechanisms that control the directional zinc flow necessary for homeostasis are not well understood. In intestinal cells, the CDF-2 transporter stores zinc in LROs during excess.

The ACE inhibitor captopril inhibits ACN-1 to control dauer formation and aging.

The renin-angiotensin-aldosterone system (RAAS) plays a well-characterized role regulating blood pressure in mammals. Pharmacological and genetic manipulation of the RAAS has been shown to extend lifespan in Caenorhabditis elegans, Drosophila and rodents, but its mechanism is not well defined. Here, we investigate the angiotensin-converting enzyme (ACE) inhibitor drug captopril, which extends lifespan in worms and mice.

The ACE-inhibitor drug captopril inhibits ACN-1 to control dauer formation and aging.

Unlabelled: The renin-angiotensin-aldosterone system (RAAS) plays a well-characterized role regulating blood pressure in mammals. Pharmacological and genetic manipulation of the RAAS has been shown to extend lifespan in , , and rodents, but its mechanism is not well defined. Here we investigate the angiotensin-converting enzyme (ACE) inhibitor drug captopril, which extends lifespan in worms and mice.

Cadmium hijacks the high zinc response by binding and activating the HIZR-1 nuclear receptor.

Cadmium is an environmental pollutant and significant health hazard that is similar to the physiological metal zinc. In , high zinc homeostasis is regulated by the high zinc activated nuclear receptor (HIZR-1) transcription factor. To define relationships between the responses to high zinc and cadmium, we analyzed transcription.

Lifespan Extension in C. elegans Caused by Bacterial Colonization of the Intestine and Subsequent Activation of an Innate Immune Response.

Mechanisms that control aging are important yet poorly defined. To discover longevity control genes, we performed a forward genetic screen for delayed reproductive aging in C. elegans.

A pathway for low zinc homeostasis that is conserved in animals and acts in parallel to the pathway for high zinc homeostasis.

The essential element zinc plays critical roles in biology. High zinc homeostasis mechanisms are beginning to be defined in animals, but low zinc homeostasis is poorly characterized. We investigated low zinc homeostasis in Caenorhabditis elegans because the genome encodes 14 evolutionarily conserved Zrt, Irt-like protein (ZIP) zinc transporter family members.

The Nuclear Receptor HIZR-1 Uses Zinc as a Ligand to Mediate Homeostasis in Response to High Zinc.

Nuclear receptors were originally defined as endocrine sensors in humans, leading to the identification of the nuclear receptor superfamily. Despite intensive efforts, most nuclear receptors have no known ligand, suggesting new ligand classes remain to be discovered. Furthermore, nuclear receptors are encoded in the genomes of primitive organisms that lack endocrine signaling, suggesting the primordial function may have been environmental sensing.

Conversion of the LIN-1 ETS protein of Caenorhabditis elegans from a SUMOylated transcriptional repressor to a phosphorylated transcriptional activator.

The LIN-1 ETS transcription factor plays a pivotal role in controlling cell fate decisions during development of the Caenorhabditis elegans vulva. Prior to activation of the RTK/Ras/ERK-signaling pathway, LIN-1 functions as a SUMOylated transcriptional repressor that inhibits vulval cell fate. Here we demonstrate using the yeast two-hybrid system that SUMOylation of LIN-1 mediates interactions with a protein predicted to be involved in transcriptional repression: the RAD-26 Mi-2β/CHD4 component of the nucleosome remodeling and histone deacetylation (NuRD) transcriptional repression complex.

The DAF-16 FOXO transcription factor regulates natc-1 to modulate stress resistance in Caenorhabditis elegans, linking insulin/IGF-1 signaling to protein N-terminal acetylation.

The insulin/IGF-1 signaling pathway plays a critical role in stress resistance and longevity, but the mechanisms are not fully characterized. To identify genes that mediate stress resistance, we screened for C. elegans mutants that can tolerate high levels of dietary zinc.

Histidine protects against zinc and nickel toxicity in Caenorhabditis elegans.

Zinc is an essential trace element involved in a wide range of biological processes and human diseases. Zinc excess is deleterious, and animals require mechanisms to protect against zinc toxicity. To identify genes that modulate zinc tolerance, we performed a forward genetic screen for Caenorhabditis elegans mutants that were resistant to zinc toxicity.

Simple copy number determination with reference query pyrosequencing (RQPS).

The accurate measurement of the copy number (CN) for an allele is often desired. We have developed a simple pyrosequencing-based method, reference query pyrosequencing (RQPS), to determine the CN of any allele in any genome by taking advantage of the fact that pyrosequencing can accurately measure the molar ratio of DNA fragments in a mixture that differ by a single nucleotide. The method involves the preparation of an RQPS probe, which contains two linked DNA fragments that match a reference allele with a known CN and a query allele with an unknown CN.

The cation diffusion facilitator gene cdf-2 mediates zinc metabolism in Caenorhabditis elegans.

Zinc is essential for many cellular processes. To use Caenorhabditis elegans to study zinc metabolism, we developed culture conditions allowing full control of dietary zinc and methods to measure zinc content of animals. Dietary zinc dramatically affected growth and zinc content; wild-type worms survived from 7 microm to 1.

The anticonvulsant ethosuximide disrupts sensory function to extend C. elegans lifespan.

Ethosuximide is a medication used to treat seizure disorders in humans, and we previously demonstrated that ethosuximide can delay age-related changes and extend the lifespan of the nematode Caenorhabditis elegans. The mechanism of action of ethosuximide in lifespan extension is unknown, and elucidating how ethosuximide functions is important for defining endogenous processes that influence lifespan and for exploring the potential of ethosuximide as a therapeutic for age-related diseases. To identify genes that mediate the activity of ethosuximide, we conducted a genetic screen and identified mutations in two genes, che-3 and osm-3, that cause resistance to ethosuximide-mediated toxicity.

Identification of mutations in Caenorhabditis elegans that cause resistance to high levels of dietary zinc and analysis using a genomewide map of single nucleotide polymorphisms scored by pyrosequencing.

Zinc plays many critical roles in biological systems: zinc bound to proteins has structural and catalytic functions, and zinc is proposed to act as a signaling molecule. Because zinc deficiency and excess result in toxicity, animals have evolved sophisticated mechanisms for zinc metabolism and homeostasis. However, these mechanisms remain poorly defined.