Tim22, the essential core of the mitochondrial protein insertion complex, forms a voltage-activated and signal-gated channel

Mol Cell. 2002 Feb;9(2):363-73. doi: 10.1016/s1097-2765(02)00446-x.


The protein insertion complex of the mitochondrial inner membrane is crucial for import of the numerous multitopic membrane proteins with internal targeting signals. Little is known about the molecular mechanism of this complex, including whether it forms a real channel or merely acts as scaffold for protein insertion. We report the unexpected observation that Tim22 is the only essential membrane-integrated subunit of the complex. Reconstituted Tim22 forms a hydrophilic, high-conductance channel with distinct opening states and pore diameters. The channel is voltage-activated and specifically responds to an internal targeting signal, but not to presequences. Thus, a protein insertion complex can combine three essential functions, signal recognition, channel formation, and energy transduction, in one central component.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Energy Metabolism
  • Gene Deletion
  • Haploidy
  • Intracellular Membranes / chemistry
  • Intracellular Membranes / physiology*
  • Ion Channel Gating / physiology*
  • Ion Channels / chemistry
  • Ion Channels / genetics
  • Ion Channels / physiology*
  • Liposomes
  • Membrane Potentials / physiology
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Membrane Transport Proteins*
  • Mitochondria / chemistry
  • Mitochondria / physiology*
  • Mitochondrial Membrane Transport Proteins*
  • Polymerase Chain Reaction
  • Protein Conformation
  • Protein Sorting Signals / physiology*
  • Recombinant Fusion Proteins / physiology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / physiology*
  • Structure-Activity Relationship


  • Carrier Proteins
  • Ion Channels
  • Liposomes
  • Membrane Proteins
  • Membrane Transport Proteins
  • Mitochondrial Membrane Transport Proteins
  • Protein Sorting Signals
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • TIM22 protein, S cerevisiae
  • TIM54 protein, S cerevisiae