ArticleJournal of molecular histology2025
ALKBH5-mediated RNA N6-methyladenosine demethylation protects against myocardial I/R-induced injury via FSP1-dependent inhibition of ferroptosis.
Article in Journal of molecular histology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed.
- SIRT1 in Cardiac Diseases: Molecular Mechanisms, Therapeutic Potential, and Future Directions.International journal of molecular sciences · 2026Review
- Ferroptosis suppressor protein 1-mediated ferroptosis suppression in sepsis: non-canonical antioxidant pathways, inflammatory regulation, and therapeutic perspectives.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Myocardial ischemia/reperfusion (I/R) injury represents a major clinical challenge, and ferroptosis has been identified as a crucial mechanism of cardiomyocyte death. While RNA N6-methyladenosine (m6A) modification is a dynamic regulator of gene expression, its role in myocardial I/R injury remains poorly defined. This study investigates the function of the m6A demethylase ALKBH5 and its underlying mechanism in counteracting ferroptosis during I/R injury. Using both ex vivo Langendorf I/R model, in vivo mouse I/R model and in vitro cardiomyocyte hypoxia/reoxygenation (H/R) models, we found that ALKBH5 expression was significantly downregulated, leading to global RNA m6A hypermethylation. ALKBH5 overexpression conferred robust cardioprotection, improving cardiac function, and reducing infarct size in mice, while enhancing cell viability and preserving mitochondrial membrane potential in cardiomyocytes. Mechanistically, RNA sequencing and mechanistic studies revealed that ALKBH5 directly binds to and demethylates m6A modifications on the mRNA of ferroptosis suppressor protein 1 (FSP1), thereby enhancing its mRNA stability and protein expression. The upregulation of FSP1 inhibited ferroptosis, as evidenced by reduced lipid peroxidation, iron overload, and reactive oxygen species accumulation, alongside increased levels of glutathione peroxidase 4 (GPX4). Crucially, the protective effects of ALKBH5 were mimicked by the ferroptosis inhibitor ferrostatin-1 and were completely abolished by FSP1 knockdown. Our findings unveil a novel ALKBH5/m6A/FSP1 signaling axis that critically suppresses ferroptosis, highlighting the therapeutic potential of targeting epitranscriptomic mechanisms for the treatment of ischemic heart disease.
Indexed as
Identifiers
41284055What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.