Mitochondrial Stress Signalling: HTRA2 and Parkinson's Disease

Figure 2

Modulation of mitochondrial quality control by the p38 stress kinase. When mitochondrial stress occurs, ROS production results in the activation of p38. Through its downstream effectors, PINK1 and CDK5, this pathway results in an increase in the proteolytic activity of mitochondrial HTRA2, which in turn contributes to the suppression of mitochondrial damage by enhancing protein quality control. By promoting the recruitment of cytosolic parkin to damaged mitochondria, PINK1 can also contribute to the clearance of these organelles through mitophagy. Antioxidant systems modulate the levels of ROS and can therefore affect signalling from p38 to either PINK1 or CDK5. Yellow: mitochondrial proteins; cyan: cytosolic proteins.