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Intracellular Trafficking and Catabolism of Free Heme: Physiological Roles and Relevance to Pathological Mechanisms

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 30 August 2025 | Viewed by 987

Special Issue Editor


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Guest Editor
Department of Bioscience and Bioinformatics, Graduate School of Computer Science and Systems Engineering, Kyushu Institute of Technology, Iizuka 820-8502, Japan
Interests: biochemistry; free heme; molecular biology

Special Issue Information

Dear Colleagues,

Hemes, iron–porphyrin complexes, are known as prosthetic groups of hemoproteins and have been extensively studied in terms of their biosynthesis, intracellular transport, and catabolism across all organisms. Recently, free hemes, unbound to hemoproteins, have emerged as regulators of various proteins. These observations strongly suggest that free heme may act as an intracellular signaling messenger, implicating the existence of complex intracellular traffic and transport mechanisms involved in the spatiotemporal relocation of the hemoprotein-unbound form of heme. However, the mechanisms governing the intracellular trafficking and transport of heme remain unclear. Moreover, excess heme within the intracellular environment undergoes rapid degradation, leading to the generation of reactive oxygen species by the unbound heme form. While heme-catabolizing enzymes are believed to protect cells from oxidative stress by converting heme to biliverdin, non-canonical roles for heme-catabolizing mechanism have only been suggested recently. The objective of this Special Issue is to collect new findings on the intracellular transport and trafficking of free heme, the mechanisms of heme degradation, and the pathological mechanisms related to these processes.

Dr. Junichi Taira
Guest Editor

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Keywords

  • heme oxygenase
  • heme metabolism
  • heme chaperon
  • free heme (labile heme)
  • cytochrome P450 reductase
  • reactive oxygen species
  • carbon monoxide
 

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Published Papers (1 paper)

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Research

13 pages, 1223 KiB  
Article
Heme Regulatory Motif of Heme Oxygenase-2 Is Involved in the Interaction with NADPH–Cytochrome P450 Reductase and Regulates Enzymatic Activity
by Masakazu Sugishima, Tomoichiro Kusumoto, Hideaki Sato, Hiroshi Sakamoto, Yuichiro Higashimoto, Ken Yamamoto and Junichi Taira
Int. J. Mol. Sci. 2025, 26(5), 2318; https://doi.org/10.3390/ijms26052318 - 5 Mar 2025
Viewed by 579
Abstract
Mammalian heme oxygenase (HO) catalyzes heme degradation using reducing equivalents supplied by NADPH–cytochrome P450 reductase (CPR). The tertiary structure of the catalytic domain of a constitutively expressed isoform of HO, HO-2, resembles that of the inductive isoform, HO-1, whereas HO-2 has two heme [...] Read more.
Mammalian heme oxygenase (HO) catalyzes heme degradation using reducing equivalents supplied by NADPH–cytochrome P450 reductase (CPR). The tertiary structure of the catalytic domain of a constitutively expressed isoform of HO, HO-2, resembles that of the inductive isoform, HO-1, whereas HO-2 has two heme regulatory motifs (HRM) at the proximal portion of the C-terminus, where the disulfide linkage reflects cellular redox conditions and the second heme binding site is located. Here, we report the results of crosslinking experiments, which suggest that HRM is located near the FMN-binding domain of the CPR when it is complexed with HO-2. The enzymatic assay and reduction kinetics results suggest that heme-bound HRM negatively regulates HO-2 activity in vitro. Cellular redox conditions and free heme concentrations may regulate HO-2 activity. Full article
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