ArticleProceedings of the National Academy of Sciences of the United States of America2010
GAPDH regulates cellular heme insertion into inducible nitric oxide synthase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
76 citing papers in PubMed, 146 citations in OpenAlex.
- NO modulates human airway smooth muscle function by altering glucose-6-phosphate dehydrogenase effects on sGC function in asthma.Redox biology · 2026Article
- Regulatory interplay between nitric oxide and heme in redox signaling and inflammation.Redox biology · 2026Review
- Structure and dynamics of a multidomain nitric oxide synthase regulated by a C2 domain.Science advances · 2026Article
- Heme and CO metabolism by the canonical human heme oxygenases.Journal of inorganic biochemistry · 2026Review
- Cell death modulation dictates tissue-specific tropism of lumpy skin disease virus.PLoS pathogens · 2026Article
- Key roles of GAPDH, Hsp90, and NO in heme trafficking.Journal of inorganic biochemistry · 2026Review
- Heme allocation in eukaryotic cells relies on mitochondrial heme export through FLVCR1b to cytosolic GAPDH.Nature communications · 2025Article
- GAPDH heme delivery to Indoleamine 2,3-dioxygenase 1 involves their complex formation and complementary charge pairing at the protein-protein interface.The Journal of biological chemistry · 2025Article
- 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
- Heme utilization by the enterococci.FEMS microbes · 2024Review
- A global view of the human post-translational modification landscape.The Biochemical journal · 2023Review
- GAPDH facilitates homologous recombination repair by stabilizing RAD51 in an HDAC1-dependent manner.EMBO reports · 2023Article
- Notes from the Underground: Heme Homeostasis inBiomolecules · 2023Review
- Article
- TgKDAC4: A Unique Deacetylase ofMicroorganisms · 2023Article
- Depletion assisted hemin affinity (DAsHA) proteomics reveals an expanded landscape of heme-binding proteins in the human proteome.Metallomics : integrated biometal science · 2023Article
- Thiol catalyzed formation of NO-ferroheme regulates canonical intravascular NO signaling.Research square · 2023Article
- New roles for GAPDH, Hsp90, and NO in regulating heme allocation and hemeprotein function in mammals.Biological chemistry · 2022Review
- Heme delivery to heme oxygenase-2 involves glyceraldehyde-3-phosphate dehydrogenase.Biological chemistry · 2022Article
- GAPDH mediates drug resistance and metabolism in Plasmodium falciparum malaria parasites.PLoS pathogens · 2022Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Heme proteins play essential roles in biology, but little is known about heme transport inside mammalian cells or how heme is inserted into soluble proteins. We recently found that nitric oxide (NO) blocks cells from inserting heme into several proteins, including cytochrome P450s, hemoglobin, NO synthases, and catalase. This finding led us to explore the basis for NO inhibition and to identify cytosolic proteins that may be involved, using inducible NO synthase (iNOS) as a model target. Surprisingly, we found that GAPDH plays a key role. GAPDH was associated with iNOS in cells. Pure GAPDH bound tightly to heme or to iNOS in an NO-sensitive manner. GAPDH knockdown inhibited heme insertion into iNOS and a GAPDH mutant with defective heme binding acted as a dominant negative inhibitor of iNOS heme insertion. Exposing cells to NO either from a chemical donor or by iNOS induction caused GAPDH to become S-nitrosylated at Cys152. Expressing a GAPDH C152S mutant in cells or providing a drug to selectively block GAPDH S-nitrosylation both made heme insertion into iNOS resistant to the NO inhibition. We propose that GAPDH delivers heme to iNOS through a process that is regulated by its S-nitrosylation. Our findings may uncover a fundamental step in intracellular heme trafficking, and reveal a mechanism whereby NO can govern the process.
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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.