FIGURE 3.

Regulation of PINK1. A: newly synthesized PINK1 is immediately imported into healthy mitochondria with an intact membrane potential (ΔΨ) by the TOM/TIM import machinery. PINK1 undergoes proteolytic cleavage by the mitochondrial intramembrane protease PARL. The cleaved PINK1 retrotranslocates to the cytosol where it is subjected to ubiquitination by E3 ubiquitin ligases UBR1, UBR2, and UBR4 and proteasomal degradation. B: upon mitochondrial damage and loss of ΔΨ, import of PINK1 is abrogated, and it accumulates on the outer mitochondrial membrane which leads to recruitment of Parkin.