Fig. 8: Working model. | Cell Death Discovery

Fig. 8: Working model.

From: ATP6AP2 knockdown in cardiomyocyte deteriorates heart function via compromising autophagic flux and NLRP3 inflammasome activation

Fig. 8

ATP6AP2, maintaining lysosomal acidification function. When ATP6AP2 was knockdown, cardiomyocyte autophagic flux and mitophagy were blocked. Further leads to the accumulation of dysfunctional mitochondria, increasing reactive oxygen species (ROS), or mitochondrial ROS. Meanwhile, accumulated ROS activates the NLRP3 inflammasome and leads to heart failure. Promoting autophagosome formation via Rapamycin increase NLRP3 activation in shR-ATP6AP2-transfected cardiomyocytes. Conversely, slowing autophagy initiation by 3-MA partially reduces ROS and activation of NLRP3 in shR-ATP6AP2-transfected cardiomyocytes. Green solid arrows show the normal autophagic flux. Arrows in dotted orange indicate that knockdown of ATP6AP2 gene blocks autophagic flux, accumulated undigested mitochondria trigger ROS and NLRP3.

Back to article page