ArticleThe Journal of biological chemistry2012
Topologically conserved residues direct heme transport in HRG-1-related proteins.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 68 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- A conserved vesicular circuit enables metabolic adaptation and maintains systemic heme homeostasis.bioRxiv : the preprint server for biology · 2026Article
- A cell-nonautonomous heme acquisition pathway enables erythroid hemoglobinization under stress.Science (New York, N.Y.) · 2026Article
- Bafilomycin A1 is a promising therapeutic agent against T. spiralis infection by inhibiting the heme-transporting ATP6V0C/HRG-1 complex.PLoS pathogens · 2026Article
- A cell-nonautonomous heme acquisition pathway enables erythroid hemoglobinization under stress.bioRxiv : the preprint server for biology · 2026Article
- Heme limitation induces LHR2, an essential gene for Leishmania pathogenesis.PLoS pathogens · 2026Article
- Article
- Exploring age-related iron dysregulation: effects on longevity, body size, and behavior in C. elegans.Experimental gerontology · 2025Article
- Molecular Mechanisms of Iron Metabolism and Overload.Biomedicines · 2025Review
- Heme and immunity: The heme oxygenase dichotomy.Journal of inorganic biochemistry · 2025Review
- Lifespan regulation by targeting heme signaling in yeast.GeroScience · 2024Article
- The mrp-3 gene is involved in haem efflux and detoxification in a blood-feeding nematode.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
- Article
- Lifespan regulation by targeting heme signaling in yeast.bioRxiv : the preprint server for biology · 2024Article
- Notes from the Underground: Heme Homeostasis inBiomolecules · 2023Review
- Haem transporter HRG-1 is essential in the barber's pole worm and an intervention target candidate.PLoS pathogens · 2023Article
- Molecular Mechanisms of Iron and Heme Metabolism.Annual review of nutrition · 2022Review
- A Recap of Heme Metabolism towards Understanding Protoporphyrin IX Selectivity in Cancer Cells.International journal of molecular sciences · 2022Review
- Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Caenorhabditis elegans and human HRG-1-related proteins are conserved, membrane-bound permeases that bind and translocate heme in metazoan cells via a currently uncharacterized mechanism. Here, we show that cellular import of heme by HRG-1-related proteins from worms and humans requires strategically located amino acids that are topologically conserved across species. We exploit a heme synthesis-defective Saccharomyces cerevisiae mutant to model the heme auxotrophy of C. elegans and demonstrate that, under heme-deplete conditions, the endosomal CeHRG-1 requires both a specific histidine in the predicted second transmembrane domain (TMD2) and the FARKY motif in the C terminus tail for heme transport. By contrast, the plasma membrane CeHRG-4 transports heme by utilizing a histidine in the exoplasmic (E2) loop and the FARKY motif. Optimal activity under heme-limiting conditions, however, requires histidine in the E2 loop of CeHRG-1 and tyrosine in TMD2 of CeHRG-4. An analogous system exists in humans, because mutation of the synonymous histidine in TMD2 of hHRG-1 eliminates heme transport activity, implying an evolutionary conserved heme transport mechanism that predates vertebrate origins. Our results support a model in which heme is translocated across membranes facilitated by conserved amino acids positioned on the exoplasmic, cytoplasmic, and transmembrane regions of HRG-1-related proteins. These findings may provide a framework for understanding the structural basis of heme transport in eukaryotes and human parasites, which rely on host heme for survival.
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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.