ArticlePLoS biology2017
The Nuclear Receptor HIZR-1 Uses Zinc as a Ligand to Mediate Homeostasis in Response to High Zinc.
Article in PLoS biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Lysosome-related organelles employ divergent mechanisms to modulate cytosolic zinc homeostasis.PLoS genetics · 2026Article
- Worming out defence strategies: mechanisms of immunity through the lens of genetic screens in C. elegans.Heredity · 2026Review
- Zinc excess promotes lysosome remodeling by activating HLH-30/TFEB through the action of the high zinc sensor HIZR-1.bioRxiv : the preprint server for biology · 2026Article
- A new set of combinatorial dimeric codes for nuclear hormone receptor-target gene specificity.Nucleic acids research · 2026Article
- A single high-zinc activation enhancer can control two genes oriented head-to-head in Caenorhabditis elegans.G3 (Bethesda, Md.) · 2025Article
- Chemical Genetics inACS chemical biology · 2024Article
- Lysosome-related organelles contain an expansion compartment that mediates delivery of zinc transporters to promote homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mediator subunit MDT-15 promotes expression of propionic acid breakdown genes to prevent embryonic lethality in Caenorhabditis elegans.G3 (Bethesda, Md.) · 2023Article
- Article
- Cadmium alters whole animal ionome and promotes the re-distribution of iron in intestinal cells ofFrontiers in physiology · 2023Article
- Cadmium hijacks the high zinc response by binding and activating the HIZR-1 nuclear receptor.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Nutritive Manganese and Zinc Overdosing in Aging C. elegans Result in a Metallothionein-Mediated Alteration in Metal Homeostasis.Molecular nutrition & food research · 2021Article
- Zinc homeostasis and signaling in the roundworm C. elegans.Biochimica et biophysica acta. Molecular cell research · 2021Review
- Natural variation in the sequestosome-related gene, sqst-5, underlies zinc homeostasis in Caenorhabditis elegans.PLoS genetics · 2020Article
- Mediator subunit MDT-15/MED15 and Nuclear Receptor HIZR-1/HNF4 cooperate to regulate toxic metal stress responses in Caenorhabditis elegans.PLoS genetics · 2019Article
- Natural products as chemical tools to dissect complex biology in C. elegans.Current opinion in chemical biology · 2019Review
- Biogenesis of zinc storage granules inThe Journal of experimental biology · 2018Article
- Zinc transporters belonging to the Cation Diffusion Facilitator (CDF) family have complementary roles in transporting zinc out of the cytosol.PLoS genetics · 2018Article
- A pathway for low zinc homeostasis that is conserved in animals and acts in parallel to the pathway for high zinc homeostasis.Nucleic acids research · 2017Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
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. Here we describe a novel Caenorhabditis elegans nuclear receptor, HIZR-1, that is a high zinc sensor in an animal and the master regulator of high zinc homeostasis. The essential micronutrient zinc acts as a HIZR-1 ligand, and activated HIZR-1 increases transcription of genes that promote zinc efflux and storage. The results identify zinc as the first inorganic molecule to function as a physiological ligand for a nuclear receptor and direct environmental sensing as a novel function of nuclear receptors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.