Structure of the mitochondrial import gate reveals distinct preprotein paths

Nature. 2019 Nov;575(7782):395-401. doi: 10.1038/s41586-019-1680-7. Epub 2019 Oct 10.


The translocase of the outer mitochondrial membrane (TOM) is the main entry gate for proteins1-4. Here we use cryo-electron microscopy to report the structure of the yeast TOM core complex5-9 at 3.8-Å resolution. The structure reveals the high-resolution architecture of the translocator consisting of two Tom40 β-barrel channels and α-helical transmembrane subunits, providing insight into critical features that are conserved in all eukaryotes1-3. Each Tom40 β-barrel is surrounded by small TOM subunits, and tethered by two Tom22 subunits and one phospholipid. The N-terminal extension of Tom40 forms a helix inside the channel; mutational analysis reveals its dual role in early and late steps in the biogenesis of intermembrane-space proteins in cooperation with Tom5. Each Tom40 channel possesses two precursor exit sites. Tom22, Tom40 and Tom7 guide presequence-containing preproteins to the exit in the middle of the dimer, whereas Tom5 and the Tom40 N extension guide preproteins lacking a presequence to the exit at the periphery of the dimer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cryoelectron Microscopy*
  • Mitochondria / chemistry
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure*
  • Mitochondrial Membrane Transport Proteins / chemistry*
  • Mitochondrial Membrane Transport Proteins / metabolism*
  • Mitochondrial Membrane Transport Proteins / ultrastructure
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Models, Molecular
  • Phospholipids / metabolism
  • Protein Multimerization
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae / ultrastructure
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / ultrastructure


  • MIA40 protein, S cerevisiae
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Phospholipids
  • Saccharomyces cerevisiae Proteins
  • TOM5 protein, S cerevisiae
  • TOM6 protein, S cerevisiae
  • Tom40 protein, S cerevisiae