Heart failure & cardiomyopathies
Loss of STMP1 Perturbs Mitochondrial Cristae and Drives Cellular Inflammation and Heart Failure
Authors' conclusion
Our work reveals a mechanism connecting the micropeptide STMP1 to mitochondrial cristae architecture and cardiomyocyte cellular inflammation, both of which are present as potential drivers of heart failure and cardiac aging.
Study context
- Population
- Mice (cardiomyocyte-specific Stmp1 knockout); aged mouse and human hearts
- Comparison
- Cardiomyocyte-specific Stmp1-KO vs wild-type mice
Methodological detailscardiomyocyte-specific knockout mouse, AAV9-mediated gene restoration
- Cardiomyocyte-specific knockout mouse
- AAV9-mediated gene restoration
Main finding
As reported in the abstract
- STMP1 downregulated specifically in cardiomyocytes, not other cardiac cell types, in aged mice and humans
- Genetic loss of Stmp1 in cardiomyocytes resulted in HF in vivo
- STMP1 interacts with components of the cristae organizing complexes MICOS and SAM
- With Stmp1 loss: mitochondrial cristae destabilised, mitochondrial DNA mislocalised to cytosol, cGAS-STING pathway activated, with cellular inflammation and cardiomyocyte death
- Restoration of wild-type Stmp1 or STING inhibition significantly rescued cardiac function in vivo
Original publication
Loss of STMP1 Perturbs Mitochondrial Cristae and Drives Cellular Inflammation and Heart Failure. Circulation. Published 10 June 2026. doi:10.
Summarised from the published abstract; every number is checked against it