Therapeutic Targeting of the Mitochondrial Dysfunction-PANoptosis Axis: Mechanistic Insights and Emerging Strategies - PubMed
4 hours ago
- #PANoptosis
- #Therapeutic Strategies
- #Mitochondrial Dysfunction
- Mitochondria regulate cellular homeostasis through energy production, metabolic integration, and signaling.
- Mitochondrial dysfunction triggers PANoptosis, a coordinated inflammatory cell death pathway combining pyroptosis, apoptosis, and necroptosis.
- PANoptosis is executed by multiprotein complexes called PANoptosomes, activated by sensors like ZBP1, AIM2, and NLRC5.
- Mitochondrial danger signals, such as ROS and mtDNA, act as upstream triggers for PANoptosis.
- ROS oxidizes and activates necroptotic mediators like RIPK1, while mtDNA engages innate immune sensors (cGAS-STING, inflammasomes).
- Defects in mitochondrial processes (oxidative phosphorylation, dynamics, mitophagy) exacerbate inflammatory signals, promoting PANoptosis.
- The mitochondrial-PANoptosis axis is implicated in various diseases.
- Therapeutic strategies targeting mitochondrial integrity or PANoptotic components show promise for reducing inflammation and cell loss.