ArticleThe Journal of biological chemistry2020
Heme oxygenase-2 is post-translationally regulated by heme occupancy in the catalytic site.
Article in The Journal of biological chemistry, 2020. 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, 29 citations in OpenAlex.
- Mitochondria-ER contacts function as an iron supply hub.Nature cell biology · 2026Article
- Predominance of Biliverdin over Bilirubin in Human Seminal Plasma.Biomolecules · 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
- Regional variations in allergen-induced airway inflammation correspond to changes in soluble guanylyl cyclase heme and expression of heme oxygenase-1.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Review
- Heme oxygenase 2 genetic variants alter hormonal and metabolic traits in polycystic ovary syndrome.Endocrine connections · 2024Article
- Heme Oxygenase-1 and Its Role in Colorectal Cancer.Antioxidants (Basel, Switzerland) · 2023Review
- 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
- A glance through the effects of CD4Computational and structural biotechnology journal · 2023Review
- 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
- Heme Oxygenase-1: An Anti-Inflammatory Effector in Cardiovascular, Lung, and Related Metabolic Disorders.Antioxidants (Basel, Switzerland) · 2022Review
- Phylogeny of the HO family in cyprinus carpio and the response of the HO-1 gene to adding Bacillus coagulans in feed under CdFish physiology and biochemistry · 2022Article
- Regulation of protein function and degradation by heme, heme responsive motifs, and CO.Critical reviews in biochemistry and molecular biology · 2022Review
- Review
- An Analysis of the Multifaceted Roles of Heme in the Pathogenesis of Cancer and Related Diseases.Cancers · 2021Review
- Unravelling the mechanisms controlling heme supply and demand.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Significance of Heme and Heme Degradation in the Pathogenesis of Acute Lung and Inflammatory Disorders.International journal of molecular sciences · 2021Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Heme oxygenase-2 (HO2) and -1 (HO1) catalyze heme degradation to biliverdin, CO, and iron, forming an essential link in the heme metabolism network. Tight regulation of the cellular levels and catalytic activities of HO1 and HO2 is important for maintaining heme homeostasis. HO1 expression is transcriptionally regulated; however, HO2 expression is constitutive. How the cellular levels and activity of HO2 are regulated remains unclear. Here, we elucidate the mechanism of post-translational regulation of cellular HO2 levels by heme. We find that, under heme-deficient conditions, HO2 is destabilized and targeted for degradation, suggesting that heme plays a direct role in HO2 regulation. HO2 has three heme binding sites: one at its catalytic site and the others at its two heme regulatory motifs (HRMs). We report that, in contrast to other HRM-containing proteins, the cellular protein level and degradation rate of HO2 are independent of heme binding to the HRMs. Rather, under heme deficiency, loss of heme binding to the catalytic site destabilizes HO2. Consistently, an HO2 catalytic site variant that is unable to bind heme exhibits a constant low protein level and an enhanced protein degradation rate compared with the WT HO2. Finally, HO2 is degraded by the lysosome through chaperone-mediated autophagy, distinct from other HRM-containing proteins and HO1, which are degraded by the proteasome. These results reveal a novel aspect of HO2 regulation and deepen our understanding of HO2's role in maintaining heme homeostasis, paving the way for future investigation into HO2's pathophysiological role in heme deficiency response.
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Registered trials
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