The nucleotide exchange factor MGE exerts a key function in the ATP-dependent cycle of mt-Hsp70-Tim44 interaction driving mitochondrial protein import

EMBO J. 1996 Nov 1;15(21):5796-803.

Abstract

Import of preproteins into the mitochondrial matrix is driven by the ATP-dependent interaction of mt-Hsp70 with the peripheral inner membrane import protein Tim44 and the preprotein in transit. We show that Mge1p, a co-chaperone of mt-Hsp70, plays a key role in the ATP-dependent import reaction cycle in yeast. Our data suggest a cycle in which the mt-Hsp70-Tim44 complex forms with ATP: Mge1p promotes assembly of the complex in the presence of ATP. Hydrolysis of ATP by mt-Hsp70 occurs in complex with Tim44. Mge1p is then required for the dissociation of the ADP form of mt-Hsp70 from Tim44 after release of inorganic phosphate but before release of ADP. ATP hydrolysis and complex dissociation are accompanied by tight binding of mt-Hsp70 to the preprotein in transit. Subsequently, the release of mt-Hsp70 from the polypeptide chain is triggered by Mge1p which promotes release of ADP from mt-Hsp70. Rebinding of ATP to mt-Hsp70 completes the reaction cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Biological Transport, Active
  • Carrier Proteins / metabolism*
  • Cations, Monovalent / metabolism
  • Escherichia coli / genetics
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Macromolecular Substances
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins*
  • Mitochondria / metabolism*
  • Mitochondrial Membrane Transport Proteins*
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Models, Biological
  • Molecular Chaperones
  • Mutation
  • Nucleotides / metabolism
  • Phosphates / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*

Substances

  • Carrier Proteins
  • Cations, Monovalent
  • Fungal Proteins
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • MGE1 protein, S cerevisiae
  • Macromolecular Substances
  • Membrane Proteins
  • Membrane Transport Proteins
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Molecular Chaperones
  • Nucleotides
  • Phosphates
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • TIM44 protein, S cerevisiae
  • Adenosine Triphosphate