ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2022
GAPDH is involved in the heme-maturation of myoglobin and hemoglobin.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Heme as a versatile signaling molecule: Coordinating mitochondrial metabolism with global cellular responses.The Journal of biological chemistry · 2026Review
- Production of Recombinant Hemoglobin inFoods (Basel, Switzerland) · 2026Article
- Dual role of Japanese encephalitis virus fusion loop peptide antibodies in Zika virus infection.PLoS neglected tropical diseases · 2026Article
- Heme and CO metabolism by the canonical human heme oxygenases.Journal of inorganic biochemistry · 2026Review
- Key roles of GAPDH, Hsp90, and NO in heme trafficking.Journal of inorganic biochemistry · 2026Review
- Stage-specific TRIM10 expression regulates erythroid maturation.EMBO reports · 2025Article
- Digital Microfluidics-Driven Cell-Free Protein Synthesis Platform Reveals Expression and Stability Determinants for Phytoglobins and Cysteine-to-Alanine Substituted Variants.Antioxidants (Basel, Switzerland) · 2025Article
- Class 1 Sugar Beet Phytoglobin Shows Strong Affinity to Glyceraldehyde-3-Phosphate Dehydrogenase and DNA In Vitro.International journal of molecular sciences · 2025Article
- 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
- Transferrin receptors.Experimental & molecular medicine · 2025Review
- Construction of a Plasmid-FreeMetabolites · 2025Article
- Metabolic engineering of yeast to efficiently synthesize heme and hemoproteins: recent advance and prospects.FEMS yeast research · 2025Review
- Design patterns of biological cells.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Review
- A natural heme deficiency exists in biology that allows nitric oxide to control heme protein functions by regulating cellular heme distribution.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- Depletion assisted hemin affinity (DAsHA) proteomics reveals an expanded landscape of heme-binding proteins in the human proteome.Metallomics : integrated biometal science · 2023Article
- Heme delivery to heme oxygenase-2 involves glyceraldehyde-3-phosphate dehydrogenase.Biological chemistry · 2022Article
- New roles for GAPDH, Hsp90, and NO in regulating heme allocation and hemeprotein function in mammals.Biological chemistry · 2022Review
- Article
- A Recap of Heme Metabolism towards Understanding Protoporphyrin IX Selectivity in Cancer Cells.International journal of molecular sciences · 2022Review
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7 authors at 1 institution in 1 country.
Funding
Abstract
GAPDH, a heme chaperone, has been previously implicated in the incorporation of heme into iNOS and soluble guanylyl cyclase (sGC). Since sGC is critical for myoglobin (Mb) heme-maturation, we investigated the role of GAPDH in the maturation of this globin, as well as hemoglobins α, β, and γ. Utilizing cell culture systems, we found that overexpression of wild-type GAPDH increased, whereas GAPDH mutants H53A and K227A decreased, the heme content of Mb and Hbα and Hbβ. Overexpression of wild-type GAPDH fully recovered the heme-maturation inhibition observed with the GAPDH mutants. Partial rescue was observed by overexpression of sGCβ1 but not by overexpression of a sGCΔβ1 deletion mutant, which is unable to bind the sGCα1 subunit required to form the active sGCα1β1 complex. Wild type and mutant GAPDH was found to be associated in a complex with each of the globins and Hsp90. GAPDH at endogenous levels was found to be associated with Mb in differentiating C2C12 myoblasts, and with Hbγ or Hbα in differentiating HiDEP-1 erythroid progenitor cells. Knockdown of GAPDH in C2C12 cells suppressed Mb heme-maturation. GAPDH knockdown in K562 erythroleukemia cells suppressed Hbα and Hbγ heme-maturation as well as Hb dimerization. Globin heme incorporation was not only dependent on elevated sGCα1β1 heterodimer formation, but also influenced by iron provision and magnitude of expression of GAPDH, d-aminolevulinic acid, and FLVCR1b. Together, our data support an important role for GAPDH in the maturation of myoglobin and γ, β, and α hemoglobins.
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