CerS6 orchestrates mitochondrial-immune crosstalk via BNIP3-dependent mitophagy suppression and mtDNA-STING/NLRP3 activation in acute lung injury - PubMed
4 hours ago
- #acute lung injury
- #mitochondrial dysfunction
- #CerS6
- CerS6 is upregulated in type II alveolar epithelial cells during acute lung injury (ALI) models like LPS and CLP.
- Knockout of CerS6 in AT2 cells reduces apoptosis, inflammation, oxidative stress, and barrier disruption while preserving mitochondrial function in ALI.
- CerS6 interacts with BNIP3, inhibiting mitophagy by disrupting BNIP3-LC3 binding, leading to mtDNA release and activation of STING/NLRP3 signaling.
- CerS6 metabolite C16:0 ceramide also contributes to these effects, highlighting sphingolipid metabolism's role in linking mitochondrial stress to immune activation.
- CerS6 is identified as a key driver of mitochondrial dysfunction and redox imbalance in ALI, suggesting it and C16:0 ceramide as potential therapeutic targets.