ArticlePLoS genetics2010
Genome-wide analysis reveals novel genes essential for heme homeostasis in Caenorhabditis elegans.
Article in PLoS genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- A conserved vesicular circuit enables metabolic adaptation and maintains systemic heme homeostasis.bioRxiv : the preprint server for biology · 2026Article
- Experimental validation of RNA interference technologies for improved control of barber's pole worm.Veterinary research · 2025Article
- Molecular Mechanisms of Iron Metabolism and Overload.Biomedicines · 2025Review
- Article
- The marine environmental microbiome mediates physiological outcomes in host nematodes.BMC biology · 2024Article
- Update on heme biosynthesis, tissue-specific regulation, heme transport, relation to iron metabolism and cellular energy.Liver international : official journal of the International Association for the Study of the Liver · 2024Review
- Notes from the Underground: Heme Homeostasis inBiomolecules · 2023Review
- Molecular Mechanisms of Iron and Heme Metabolism.Annual review of nutrition · 2022Review
- Haem-responsive gene transporter enables mobilization of host haem in ticks.Open biology · 2021Article
- KinFin: Software for Taxon-Aware Analysis of Clustered Protein Sequences.G3 (Bethesda, Md.) · 2017Article
- Inter-organ signalling by HRG-7 promotes systemic haem homeostasis.Nature cell biology · 2017Article
- TheThe Journal of biological chemistry · 2017Article
- RNA-seq analyses of the midgut from blood- and serum-fed Ixodes ricinus ticks.Scientific reports · 2016Article
- Histidine residues are important for preserving the structure and heme binding to the C. elegans HRG-3 heme-trafficking protein.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2015Article
- Lessons from bloodless worms: heme homeostasis in C. elegans.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2015Article
- Heme Signaling Impacts Global Gene Expression, Immunity and Dengue Virus Infectivity in Aedes aegypti.PloS one · 2015Article
- Culturing Caenorhabditis elegans in axenic liquid media and creation of transgenic worms by microparticle bombardment.Journal of visualized experiments : JoVE · 2014Article
- Control of metazoan heme homeostasis by a conserved multidrug resistance protein.Cell metabolism · 2014Article
- Silencing of maternal heme-binding protein causes embryonic mitochondrial dysfunction and impairs embryogenesis in the blood sucking insect Rhodnius prolixus.The Journal of biological chemistry · 2013Article
- Pseudomonas aeruginosa disrupts Caenorhabditis elegans iron homeostasis, causing a hypoxic response and death.Cell host & microbe · 2013Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Heme is a cofactor in proteins that function in almost all sub-cellular compartments and in many diverse biological processes. Heme is produced by a conserved biosynthetic pathway that is highly regulated to prevent the accumulation of heme--a cytotoxic, hydrophobic tetrapyrrole. Caenorhabditis elegans and related parasitic nematodes do not synthesize heme, but instead require environmental heme to grow and develop. Heme homeostasis in these auxotrophs is, therefore, regulated in accordance with available dietary heme. We have capitalized on this auxotrophy in C. elegans to study gene expression changes associated with precisely controlled dietary heme concentrations. RNA was isolated from cultures containing 4, 20, or 500 microM heme; derived cDNA probes were hybridized to Affymetrix C. elegans expression arrays. We identified 288 heme-responsive genes (hrgs) that were differentially expressed under these conditions. Of these genes, 42% had putative homologs in humans, while genomes of medically relevant heme auxotrophs revealed homologs for 12% in both Trypanosoma and Leishmania and 24% in parasitic nematodes. Depletion of each of the 288 hrgs by RNA-mediated interference (RNAi) in a transgenic heme-sensor worm strain identified six genes that regulated heme homeostasis. In addition, seven membrane-spanning transporters involved in heme uptake were identified by RNAi knockdown studies using a toxic heme analog. Comparison of genes that were positive in both of the RNAi screens resulted in the identification of three genes in common that were vital for organismal heme homeostasis in C. elegans. Collectively, our results provide a catalog of genes that are essential for metazoan heme homeostasis and demonstrate the power of C. elegans as a genetic animal model to dissect the regulatory circuits which mediate heme trafficking in both vertebrate hosts and their parasites, which depend on environmental heme for survival.
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