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New roles for GAPDH, Hsp90, and NO in regulating heme allocation and hemeprotein function in mammals

  • Dennis J. Stuehr EMAIL logo , Yue Dai , Pranjal Biswas ORCID logo , Elizabeth A. Sweeny and Arnab Ghosh
Published/Copyright: September 26, 2022

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.


Corresponding author: Dennis J. Stuehr, Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA, E-mail:

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

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. 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.).

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

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Received: 2022-06-03
Accepted: 2022-08-17
Published Online: 2022-09-26
Published in Print: 2022-11-25

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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