SERCA2 dysfunction drives vascular calcification via coupling with TSPO-MCU at mitochondria-associated endoplasmic reticulum membranes - PubMed
6 hours ago
- #Mitochondrial Calcium
- #SERCA2
- #Vascular Calcification
- SERCA2 dysfunction, marked by oxidized Cys674, is elevated in calcified arteries of mice and CKD patients.
- SERCA2 dysfunction worsens vascular calcification, mitochondrial impairment, and calcium overload in VSMCs.
- The mechanism involves increased MAM formation, with TSPO coupling SERCA2 to the IP3R1-Grp75-VDAC1-MCU complex.
- TSPO knockdown alleviates calcification in SERCA2 dysfunction models, while TSPO overexpression aggravates it.
- Inhibiting MCU reduces mitochondrial calcium overload and mitigates calcification effects.