Regulated cycling of mitochondrial Hsp70 at the protein import channel

Science. 2003 Apr 4;300(5616):139-41. doi: 10.1126/science.1083379.


Hsp70 of the mitochondrial matrix (mtHsp70) provides a critical driving force for the import of proteins into mitochondria. Tim44, a peripheral inner-membrane protein, tethers it to the import channel. Here, regulated interactions were found to maximize occupancy of the active, adenosine 5'-triphosphate (ATP)-bound mtHsp70 at the channel through its intrinsic high affinity for Tim44, as well as through release of adenosine diphosphate (ADP)-bound mtHsp70 from Tim44 by the cofactor Mge1. A model peptide substrate rapidly released mtHsp70 from Tim44, even in the absence of ATP hydrolysis. In vivo, the analogous interaction of translocating polypeptide would release mtHsp70 from the channel. Consistent with the ratchet model of translocation, subsequent hydrolysis of ATP would trap the polypeptide, driving import by preventing its movement back toward the cytosol.

Publication types

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

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Adenosine Diphosphate / pharmacology
  • Adenosine Triphosphate / metabolism
  • Adenosine Triphosphate / pharmacology
  • Adenylyl Imidodiphosphate / pharmacology
  • Carrier Proteins / metabolism*
  • HSP70 Heat-Shock Proteins / metabolism*
  • Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / pharmacology
  • Hydrolysis
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins / metabolism
  • Membrane Transport Proteins / pharmacology
  • Mitochondria / metabolism*
  • Mitochondrial Membrane Transport Proteins*
  • Models, Biological
  • Molecular Chaperones
  • Protein Binding
  • Protein Transport
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / pharmacology


  • Carrier Proteins
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • MGE1 protein, S cerevisiae
  • Membrane Proteins
  • Membrane Transport Proteins
  • Mitochondrial Membrane Transport Proteins
  • Molecular Chaperones
  • Saccharomyces cerevisiae Proteins
  • TIM44 protein, S cerevisiae
  • Adenylyl Imidodiphosphate
  • Adenosine Diphosphate
  • Adenosine Triphosphate