| Gene | [HMOX1](/genes/hmox1) |
| UniProt | [P09601](https://www.uniprot.org/uniprot/P09601) |
| MW | 32.8 kDa |
| Location | ER membrane, microsomes |
| PDB | [1N45](https://www.rcsb.org/structure/1N45) |
Heme oxygenase-1 (HO-1), also known as heat shock protein 32 (HSP32), is the inducible isoform of heme oxygenase that catalyzes the rate-limiting step in heme degradation. HO-1 cleaves heme into biliverdin (later converted to bilirubin), carbon monoxide (CO), and free iron (Fe²⁺). As a stress-responsive enzyme activated by oxidative stress, heavy metals, and inflammation, HO-1 plays a dual role in neurodegeneration—protective through antioxidant bilirubin production but potentially harmful through iron release.
HO-1 is anchored to the endoplasmic reticulum membrane:
The enzyme requires NADPH-cytochrome P450 reductase as an electron donor for catalytic activity.
HO-1 catalyzes the oxidative degradation of heme:
HO-1 products have distinct biological activities:
| Product | Function | Neuroprotective Effect |
|---|---|---|
| Bilirubin | Antioxidant | Scavenges peroxyl radicals, more potent than vitamin E |
| Carbon monoxide | Signaling gas | Anti-inflammatory, vasodilatory, anti-apoptotic |
| Free iron | Pro-oxidant | Activates ferritin transcription (protective feedback) |
HO-1 expression is markedly increased in AD brain tissue:
The role of HO-1 in AD is complex—acute induction is protective, but chronic upregulation may exacerbate iron-mediated oxidative damage.
HO-1 is upregulated in dopaminergic neurons of the substantia nigra:
HO-1 is intimately linked to ferroptosis, an iron-dependent cell death pathway:
HO-1 expression is elevated in MS lesions:
Pharmacological inhibition may be beneficial in iron-overload conditions:
| Compound | Mechanism | Status |
|---|---|---|
| Tin protoporphyrin (SnPP) | Competitive inhibitor | Research tool |
| Zinc protoporphyrin (ZnPP) | Competitive inhibitor | Research tool |
| OB-24 | Novel inhibitor | Preclinical |
Induction may be beneficial in acute oxidative stress:
A (GT)n repeat polymorphism in the HMOX1 promoter influences expression:
| Partner | Function | Disease Relevance |
|---|---|---|
| Nrf2 | Transcriptional activator | Antioxidant response |
| Bach1 | Transcriptional repressor | Heme-dependent regulation |
| Ferritin | Iron sequestration | Iron homeostasis |
| NRF1 | Ferroptosis suppressor | Lipid peroxidation protection |
| Biliverdin reductase | Bilirubin production | Antioxidant pathway |
Smith et al. Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer's disease. Am J Pathol. 1994. ↩︎
Ham et al. Iron and lipid peroxidation in the Alzheimer's disease brain: the role of heme oxygenase-1. Amino Acids. 2015. ↩︎
Suliman et al. Mitochondrial quality control via mitophagy in heme oxygenase-1 deficient cells. Free Radic Biol Med. 2016. ↩︎
Schipper et al. Heme oxygenase-1 expression in dopaminergic neurons of the substantia nigra in Parkinson's disease. Mov Disord. 1998. ↩︎
Schipper et al. Heme oxygenase-1 and the dopamine system in Parkinson's disease. Amino Acids. 2015. ↩︎
Adedoyin et al. Heme oxygenase-1 promotes ferroptosis by increasing the labile iron pool. Cell Death Dis. 2021. ↩︎
Ayuso et al. Association between the (GT)n polymorphism of the HMOX1 gene promoter and Alzheimer's disease. J Alzheimers Dis. 2019. ↩︎