Structure of human PINK1 at a mitochondrial TOM/VDAC array

We report here the structure of human PINK1 stabilized mid-import at an array of endogenous TOM and VDAC complexes purified from human mitochondria. In our structure, two TOM core complexes are separated by a dimer of VDAC2 channels, and an inactive PINK1 dimer is inserted into the VDAC-proximal TOM40 pores, positioning the dimerized PINK1 kinase domains directly atop the VDAC channels. The structure explains how PINK1 interacts with subunits of the TOM complex and rationalizes several known EOPD patient mutations. The unexpected arrangement of TOM with VDAC suggests a structural role for VDAC channels in forming mitochondrial import arrays, and the stalled PINK1 import intermediate illuminates how a presequence import substrate is guided across the mitochondrial outer membrane.