Parkinson's disease-associated PLA2G6 protects IP3R1 protein to control ER-mitochondria tethering and Ca2+ transfer - PubMed
4 hours ago
- #Parkinson's disease
- #PLA2G6
- #ER-mitochondria tethering
- Mutations in PLA2G6 gene are linked to autosomal recessive Parkinson's disease (PD).
- PLA2G6 loss-of-function disrupts mitochondria-associated endoplasmic reticulum membrane (MAM), affecting Ca2+ transfer and energy homeostasis.
- PLA2G6 protein localizes to MAM and interacts with IP3R1-GRP75-VDAC1 complex; its deficiency destabilizes this complex, leading to IP3R1 degradation.
- Reduced ER-mitochondria contacts and impaired Ca2+ transfer result from PLA2G6 deficiency.
- A MAM linker can restore phenotypes caused by PLA2G6 loss.
- iPSCs-derived dopaminergic neurons from PD patients with PLA2G6 mutations confirm MAM disruption, highlighting its role in PD pathogenesis.
- Modulating inter-organelle contacts may be a therapeutic strategy for PD's ion channel dysfunction and energy imbalances.