Figures & data
Figure 1. The APPL1-RAB5 axis controls early endosome-mediated mitochondrial clearance and NLRP3 inflammasome activation. (A) In macrophages with the functional APPL1-RAB5 axis, the early endosomes are recruited to damaged mitochondria in response to NLRP3 inflammasome activator. APPL1+ and RAB5+ endosomes aid the delivery of damaged mitochondria to the mitophagy machinery for its degradation, thereby preventing NLRP3 inflammasome overactivation by mitochondrial-derived danger signals such as mtDNA and mtROS. (B) Defective APPL1-mediated mitophagy impairs the recruitment of RAB5 to mitochondria and the downstream mitochondrial clearance, leading to accumulation of damaged mitochondria and its associated danger signals. Elevated mitochondrial-derived danger signals trigger the hyperactivation of the NLRP3 inflammasome for the production of IL1B and IL18, thereby exacerbating inflammatory diseases such as type 2 diabetes and sepsis. (Created with BioRender.com).
