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

By Jason C. Young, N. Hoogenraad, F. Hartl. Cell, 2003

898 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/93a7a83d2f3067ef82157b3676eb7503a493f302

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Citations in the corpus

The Response to Heat Shock and Oxidative Stress in Saccharomyces cerevisiae (2012, neutral): “TOM70 TPR; mitochondrial import Young et al. (2003)”
Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. (2020, neutral): “Tom70 is one of the major import receptors in the translocase of the outer membrane (TOM) complex that recognizes and mediates the translocation of mitochondrial preproteins from the cytosol into the mitochondria in a chaperone-dependent manner (8).”
Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis. (2004, background): “TPR proteins in the outer mitochondrial membrane in addition to hFis1 include Tom20 (Iwahashi et al., 1997) and Tom70 (Young et al., 2003), both of which are involved in recruitment of other proteins to mitochondria.”
Importing Mitochondrial Proteins: Machineries and Mechanisms (2009, background): “The precursorchaperone complexes are recognized by the surface receptor Tom70, which possesses binding sites for both the precursor proteins and the chaperones (Wiedemann et al., 2001; Young et al., 2003; Wu and Sha, 2006; Zara et al., 2009).”
Mitochondrial protein import: from proteomics to functional mechanisms (2010, background): “The chaperones not only guide the precursors to mitochondria but also specifically bind to the receptor Tom70 and thus ensure a direct transfer of the precursors to the import machinery of mitochondri”
HSP90 at the hub of protein homeostasis: emerging mechanistic insights (2010, background): “, and with translocation machineries to get proteins to their proper location”
Amyloid-like aggregates sequester numerous metastable proteins with essential cellular functions. (2011, background): “For example, among the b protein interactors are mitochondrial membrane proteins such as VDAC and the ADP/ATP translocase which require chaperone protection during post-translational sorting (Young et al., 2003).”
Pathways of chaperone-mediated protein folding in the cytosol (2004, background): “In both mammals and yeast, TOM70 recognizes the precursor-protein-binding chaperones through its co-chaperone TPR-clamp domain, and this docking step is important for the transfer of the precursors to the import receptor and the mitochondrial import machiner”