Figure 2.

Main alterations of factors modulating mitophagy observed in AD and PD. In AD, Aβ accumulation upregulated PINK/Parkin pathway. Mutant human APP increases recruitment of Parkin to depolarized mitochondria. mAPP also causes upregulation of mitochondrial fission genes DRP1, and decrease of fusion genes MFN1/2 and OPA1. Tau interacts with Parkin and inhibits its translocation to defective mitochondria. Furthermore, it upregulates fission proteins and inhibits fusion proteins. In PD, defective mitophagy is determined by loss of function of Parkin, PINK1, and DJ- 1; their dysfunction is associated with high levels of ROS. Loss of LRKK2 blocks the degradation of the outer membrane protein Miro and triggers mitophagy. In this context, NIX and AMBRA, can limit the excessive production of ROS. See text for details.