Abstract
The intracellular trafficking of mitochondrial heme presents a fundamental challenge to animal cells. This article provides some background on heme allocation, discusses some of the concepts, and then reviews research done over the last decade, much in the author’s laboratory, that is uncovering unexpected and important roles for glyceraldehyde 3-phosphate dehydrogenase (GAPDH), heat shock protein 90 (hsp90), and nitric oxide (NO) in enabling and regulating the allocation of mitochondrial heme to hemeproteins that mature and function outside of the mitochondria. A model for how hemeprotein functions can be regulated in cells through the coordinate participation of GAPDH, hsp90, and NO in allocating cellular heme is presented.
Funding source: National Institute of Health Grants – Programme Grants for Applied Research
Award Identifier / Grant number: K99 HL144921
Award Identifier / Grant number: P01 HL081064
Award Identifier / Grant number: R01 GM130624
Award Identifier / Grant number: R01 HL150049
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Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Research funding: The work was supported by National Institute of Health Grants – Programme Grants for Applied Research – R01 GM130624 and P01 HL081064 (D.J.S.), R01 HL150049 (A.G.), and K99 HL144921 (E.A.S.).
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Conflict of interest statement: The authors declare no conflicts of interest regarding this article.
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© 2022 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Heme research – the past, the present and the future
- A primer on heme biosynthesis
- New roles for GAPDH, Hsp90, and NO in regulating heme allocation and hemeprotein function in mammals
- The role of host heme in bacterial infection
- Signal transduction mechanisms in heme-based globin-coupled oxygen sensors with a focus on a histidine kinase (AfGcHK) and a diguanylate cyclase (YddV or EcDosC)
- Heme delivery to heme oxygenase-2 involves glyceraldehyde-3-phosphate dehydrogenase
- Novel insights into heme binding to hemoglobin
- Extracellular hemin is a reverse use-dependent gating modifier of cardiac voltage-gated Na+ channels
- Assessment of the breadth of binding promiscuity of heme towards human proteins
- Determination of free heme in stored red blood cells with an apo-horseradish peroxidase-based assay
- Comparative studies of soluble and immobilized Fe(III) heme-peptide complexes as alternative heterogeneous biocatalysts
Articles in the same Issue
- Frontmatter
- Heme research – the past, the present and the future
- A primer on heme biosynthesis
- New roles for GAPDH, Hsp90, and NO in regulating heme allocation and hemeprotein function in mammals
- The role of host heme in bacterial infection
- Signal transduction mechanisms in heme-based globin-coupled oxygen sensors with a focus on a histidine kinase (AfGcHK) and a diguanylate cyclase (YddV or EcDosC)
- Heme delivery to heme oxygenase-2 involves glyceraldehyde-3-phosphate dehydrogenase
- Novel insights into heme binding to hemoglobin
- Extracellular hemin is a reverse use-dependent gating modifier of cardiac voltage-gated Na+ channels
- Assessment of the breadth of binding promiscuity of heme towards human proteins
- Determination of free heme in stored red blood cells with an apo-horseradish peroxidase-based assay
- Comparative studies of soluble and immobilized Fe(III) heme-peptide complexes as alternative heterogeneous biocatalysts