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Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor Tom70

Cell. 2003 Jan 10;112(1):41-50. doi: 10.1016/s0092-8674(02)01250-3.

Abstract

The role of cytosolic factors in protein targeting to mitochondria is poorly understood. Here, we show that in mammals, the cytosolic chaperones Hsp90 and Hsp70 dock onto a specialized TPR domain in the import receptor Tom70 at the outer mitochondrial membrane. This interaction serves to deliver a set of preproteins to the receptor for subsequent membrane translocation dependent on the Hsp90 ATPase. Disruption of the chaperone/Tom70 recognition inhibits the import of these preproteins into mitochondria. In yeast, Hsp70 rather than Hsp90 is used in import, and Hsp70 docking is required for the formation of a productive preprotein/Tom70 complex. We outline a novel mechanism in which chaperones are recruited for a specific targeting event by a membrane-bound receptor.

Publication types

  • Comparative Study

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Amino Acid Substitution
  • Animals
  • Biological Transport, Active
  • COS Cells
  • Cytosol / enzymology
  • Fungal Proteins / chemistry
  • Fungal Proteins / metabolism*
  • HSP70 Heat-Shock Proteins / chemistry
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • HSP90 Heat-Shock Proteins / chemistry
  • HSP90 Heat-Shock Proteins / drug effects
  • HSP90 Heat-Shock Proteins / genetics
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mitochondria / metabolism*
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Models, Biological
  • Protein Binding
  • Protein Precursors / metabolism*
  • Rats
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Fungal Proteins
  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • Membrane Proteins
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Protein Precursors
  • Receptors, Cell Surface
  • Saccharomyces cerevisiae Proteins
  • TOM70 protein, S cerevisiae
  • Adenosine Triphosphatases