Figure 4.

Pink1 and Parkin in mitophagy in healthy and dysfunction mitochondria. A, In normal healthy mitochondria, Pink1 is predominantly expressed in the IMM. Pink1 is then translocated to the cytosol, where Pink1 is digested by the proteasome. Pink1 does not ubiquitinate OMM proteins and the cytosolic protein Parkin, and so Parkin is not activated. B, When mitochondria are extremely damaged, the Pink1‐Parkin pathway is activated. Pink1, instead of being degraded by the proteasome, is translocated to the OMM, which leads to its accumulation on the OMM. Pink1 phosphorylates both ubiquitin on the OMM and Parkin. The E3 ligase activity of Parkin is initiated, Parkin then ubiquitinates protein substrates, such as Miro, on the OMM, and also recruits the autophagosome to the mitochondrion for mitochondrial degradation