ALDH2/eIF3E Interaction Modulates Protein Translation Critical for Cardiomyocyte Ferroptosis in Acute Myocardial Ischemia Injury
Authors' conclusion
ALDH2*2 aggravates acute heart failure after MI by promoting the selective translation of mRNAs containing the GAGGACR motif, thereby driving cardiomyocyte ferroptosis.
Study context
- Population
- Chinese patients with acute HF after acute myocardial infarction (AMI); Myocardial infarction (MI) mouse model (LAD ligation) in wild-type, ALDH2*2 and cardiomyocyte-specific eIF3E-knockdown miceChinese cohort
- Participants
- 177 patients
- Comparison
- ALDH2*2 vs ALDH2 wild type
Main finding
As reported in the abstract
- Human ALDH2*2 carriers: more severe HF after AMI, with plasma ferroptosis features (increased bioactive lipids, decreased antioxidants such as coenzyme Q10 and BH4)
- Similar features in ALDH2*2 MI mice; ferroptosis inhibition by Fer-1 significantly improved heart function and reversed ferroptosis markers
- ALDH2*2 significantly decreased ALDH2 protein; TFRC and ACSL4 notably upregulated in infarct heart tissue
- ALDH2 binds eIF3 complex via eIF3E, preventing eIF3E-eIF4G1-mRNA assembly; ALDH2*2 deficiency releases eIF3E, driving selective translation of GAGGACR-motif mRNAs (eg, TFRC, ACSL4, UAP1) to promote ferroptosis
- Cardiomyocyte-specific eIF3E knockdown restored ALDH2*2 cardiac function by attenuating ferroptosis in MI
Original publication
ALDH2/eIF3E Interaction Modulates Protein Translation Critical for Cardiomyocyte Ferroptosis in Acute Myocardial Ischemia Injury. Circulation. Published 20 October 2025. doi:10.
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