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PMID:12526792

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Citation

Young, JC, Hoogenraad, NJ and Hartl, FU (2003) Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor Tom70. Cell 112:41-50

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.

Links

PubMed

Keywords

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; 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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:TOM70

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P07900

F

Seeded From UniProt

complete

HUMAN:HS90A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O94826

F

Seeded From UniProt

complete

HUMAN:HS90A

located_in

GO:0005829: cytosol

ECO:0000303: author statement without traceable support used in manual assertion

C

Seeded From UniProt

complete

YEAST:HSP82

involved_in

GO:0006626: protein targeting to mitochondrion

ECO:0000353: physical interaction evidence used in manual assertion

SGD:S000005065

P

Seeded From UniProt

complete

HUMAN:HS90A

involved_in

GO:0006839: mitochondrial transport

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete

HUMAN:HS90A

enables

GO:0030911: TPR domain binding

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

HUMAN:HS90A

part_of

GO:0005829: cytosol

ECO:0000303: author statement without traceable support used in manual assertion

C

Seeded From UniProt

complete


See also

References

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