The chaperone-binding activity of the mitochondrial surface receptor Tom70 protects the cytosol against mitoprotein-induced stress.
Most mitochondrial proteins are synthesized as precursors in the cytosol and post-translationally transported into mitochondria. The mitochondrial surface protein Tom70 acts at the interface of the cytosol and mitochondria. In vitro import experiments identified Tom70 as targeting receptor, particularly for hydrophobic carriers. Using in vivo methods and high-content screens, we revisit the ... question of Tom70 function and considerably expand the set of Tom70-dependent mitochondrial proteins. We demonstrate that the crucial activity of Tom70 is its ability to recruit cytosolic chaperones to the outer membrane. Indeed, tethering an unrelated chaperone-binding domain onto the mitochondrial surface complements most of the defects caused by Tom70 deletion. Tom70-mediated chaperone recruitment reduces the proteotoxicity of mitochondrial precursor proteins, particularly of hydrophobic inner membrane proteins. Thus, our work suggests that the predominant function of Tom70 is to tether cytosolic chaperones to the outer mitochondrial membrane, rather than to serve as a mitochondrion-specifying targeting receptor.
Mesh Terms:
Cytosol, Membrane Proteins, Mitochondria, Mitochondrial Precursor Protein Import Complex Proteins, Molecular Chaperones, Protein Aggregates, Protein Binding, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Stress, Physiological
Cytosol, Membrane Proteins, Mitochondria, Mitochondrial Precursor Protein Import Complex Proteins, Molecular Chaperones, Protein Aggregates, Protein Binding, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Stress, Physiological
Cell Rep
Date: Apr. 06, 2021
PubMed ID: 33826901
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