Structure of human PINK1 at a mitochondrial TOM-VDAC array

Mutations in the ubiquitin kinase PINK1 cause early-onset Parkinson's disease, but how PINK1 is stabilized at depolarized mitochondrial translocase complexes has remained poorly understood. We determined a 3.1-angstrom resolution cryo-electron microscopy structure of dimeric human PINK1 stabilized at an endogenous array of mitochondrial translocase of the outer membrane (TOM) and voltage-dependent anion channel (VDAC) complexes. Symmetric arrangement of two TOM core complexes around a central VDAC2 dimer is facilitated by TOM5 and TOM20, both of which also bind PINK1 kinase C-lobes. PINK1 enters mitochondria through the proximal TOM40 barrel of the TOM core complex, guided by TOM7 and TOM22. Our structure…