Mitochondrial flagella-like extensions (MitoFLARE) dysfunction triggers STING-mediated immune dysregulation in sepsis - PubMed
4 hours ago
- #mitochondrial dysfunction
- #cGAS-STING signaling
- #sepsis immune dysregulation
- Mitochondria in early-stage LPS treatment form flagella-like extensions (MitoFLARE) for long-distance transport via nanotube formation driven by glycosylated TRAK1 binding FHL2.
- As inflammation progresses, mitochondrial quality control deteriorates, disrupting the MICOS-SAM complex and suppressing MitoFLARE function, leading to enhanced endoplasmic reticulum-mitochondrial contacts.
- Mitochondrial outer membrane rupture occurs, releasing mtDNA into the cytoplasm, which activates cGAS-STING signaling, triggering immune dysregulation and inflammatory storms in sepsis.
- This process results in programmed cell death and organ dysfunction, highlighting the role of dysregulated mitochondrial-host symbiosis in sepsis progression.
- The study provides insights into the mechanisms of immune imbalances in sepsis and a foundation for developing targeted therapies.