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TitleStructure of human PINK1 at a mitochondrial TOM-VDAC array.
Journal, issue, pagesScience, Vol. 388, Issue 6744, Page 303-310, Year 2025
Publish dateApr 18, 2025
AuthorsSylvie Callegari / Nicholas S Kirk / Zhong Yan Gan / Toby Dite / Simon A Cobbold / Andrew Leis / Laura F Dagley / Alisa Glukhova / David Komander /
PubMed AbstractMutations 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 ...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 explains how human PINK1 is stabilized at the TOM complex and regulated by oxidation, uncovers a previously unknown TOM-VDAC assembly, and reveals how a physiological substrate traverses TOM40 during translocation.
External linksScience / PubMed:40080546
MethodsEM (single particle)
Resolution2.75 - 3.3 Å
Structure data

48083

9eih

EMDB-48083, PDB-9eih:
Import stalled PINK1 TOM complex
Method: EM (single particle) / Resolution: 3.1 Å

48084

9eii

EMDB-48084, PDB-9eii:
Import stalled PINK1 TOM complex, symmetry expanded
Method: EM (single particle) / Resolution: 2.75 Å

48085

9eij

EMDB-48085, PDB-9eij:
Import stalled PINK1 TOM complex, extended TOM20 helix class
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-PC1:
1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE / phospholipid*YM

Source
  • homo sapiens (human)
KeywordsTRANSLOCASE / PINK1 / TOM complex / VDAC

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