Mutations in Parkin and PINK1 cause early-onset Parkinson’s disease (PD). PINK1 is a kinase that acts as a sensor of mitochondrial damage and initiates Parkin-mediated quality control. Recruitment and activation of Parkin by PINK1 leads to the ubiquitination of outer mitochondrial membrane proteins and subsequent autophagic clearance of the damaged organelle¹. Our lab has been elucidating the molecular mechanisms of this pathway using proteomics and structural biology tools. Parkin is basally a cytosolic ubiquitin ligase, which adopts an auto-inhibited conformation². PINK1 phosphorylates ubiquitin³, and the resulting phospho-　ubiquitin acts as a receptor and activator for Parkin^4,5. We recently discovered that PINK1 itself requires activation via auto-phosphorylation at a single serine, which enables ubiquitin recognition⁶.

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