STING1 senses mitochondrial damage to promote mitophagy - PubMed
2 hours ago
- #Selective autophagy
- #cGAS-STING1 pathway
- #Mitochondrial quality control
- The cGAS-STING1 pathway, known for innate immunity, also plays a non-canonical role in promoting mitophagy for organelle quality control.
- Upon mitochondrial damage, STING1 is recruited to damaged mitochondria via PINK1- and VCP/p97-mediated degradation of outer membrane proteins.
- STING1 activates TBK1, which phosphorylates the mitophagy receptor OPTN at Ser177, enhancing OPTN recruitment and driving efficient mitophagy.
- Disruption of the STING1-TBK1-OPTN axis impairs mitophagy, shifting the cellular response from pro-survival mitophagy to apoptosis.
- This finding extends the cGAS-STING1 pathway's role beyond immunity to regulating selective autophagy and cell fate decisions.