Figure 7. Phosphorylation of ubiquitin on mitochondria acts on both recruitment and activation.

Accumulation of PINK1 leads to phosphorylation of ubiquitin on damaged mitochondria and recruitment of inactive parkin. Parkin can be activated through one of two ways. It can bind a second phosphorylated ubiquitin molecule or it can be phosphorylated on its Ubl domain. In the first case, the activation signal (pUb) is fixed and pre‐set, while in the second, it depends on the interaction between PINK1 and parkin. Both paths lead to a conformational change in which binding of pUb or pUbl to RING0 releases the catalytic RING2 domain (R2). Upon activation, parkin adds more ubiquitin molecules to the mitochondrial surface, which generates a positive feedback cycle of PINK1 activity and parkin recruitment. Phosphorylation sites are represented by red circles, and the parkin active‐site cysteine by yellow sphere when inactive and a star when active.