Heart failure & cardiomyopathies
FMO2 Prevents Pathological Cardiac Hypertrophy by Maintaining the ER-Mitochondria Association Through Interaction With IP3R2-Grp75-VDAC1
Authors' conclusion
Our findings reveal a key role of FMO2 in myocardial hypertrophy and that FMO2 plays a pivotal role in maintaining MAM structure and function
Study context
- Population
- Human heart tissue from patients with cardiac hypertrophy; mouse models of pathological cardiac hypertrophy; neonatal rat cardiomyocytes
Methodological detailsBulk RNA-sequencing of human hypertrophic heart tissue; MAM-targeted mass spectrometry in a mouse model; neonatal rat cardiomyocyte culture; genetic mouse models with AAV9 under the cardiac troponin T promoter
- Bulk RNA-sequencing of human hypertrophic heart tissue; MAM-targeted mass spectrometry in a mouse model; neonatal rat cardiomyocyte culture; genetic mouse models with AAV9 under the cardiac troponin T promoter
Main finding
As reported in the abstract
- FMO2, an ER-resident protein, identified as a component of MAMs structure
- FMO2 levels decreased during pathological cardiac hypertrophy
- FMO2 deletion worsened and overexpression prevented pathological HF progression in vivo
- FMO2 localizes to MAMs, binds IP3R2 within the IP3R2-Grp75-VDAC1 complex, maintaining ER-mitochondria contact and regulating mitochondrial Ca2+ signaling for bioenergetics
- Synthetic peptide enhancing ER-mitochondria contact promoted Ca2+ transfer and prevented pathological cardiac hypertrophy
Original publication
FMO2 Prevents Pathological Cardiac Hypertrophy by Maintaining the ER-Mitochondria Association Through Interaction With IP3R2-Grp75-VDAC1. Circulation. Published 9 June 2025. doi:10.
Summarised from the published abstract; every number is checked against it