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The mitochondrial surface receptor Tom70 protects the cytosol against mitoprotein-induced stress - TAH1 IP

ABSTRACT: Most mitochondrial proteins are synthesized as precursor proteins 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, we revisited the Tom70 function, confirming that it supports the biogenesis of carriers and other mitochondrial proteins which considerably expands the set of Tom70-dependent mitochondrial proteins. However, the crucial activity of Tom70 is its recruitment of cytosolic chaperones to the outer membrane. Surprisingly, tethering an unrelated chaperone-binding domain onto the mitochondrial surface complements most of the defects caused by the absence of Tom70. In vivo, small single spanning inner membrane proteins can be particularly problematic when present in excess and the chaperone-binding ability of Tom70 is crucial to suppress their proteotoxicity. Thus, the predominant function of Tom70 is more that of a cytosolic co-chaperone, and its role as mitochondria-specifying receptor apparently is of less immediate relevance.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

TISSUE(S): Cell Suspension Culture

SUBMITTER: Markus Räschle

LAB HEAD: Zuzana Storchova

PROVIDER: PXD023149 | Pride | 2021-03-26

REPOSITORIES: Pride

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The mitochondrial surface receptor Tom70 protects the cytosol against mitoprotein-induced stress

Project description:Most mitochondrial proteins are synthesized as precursor proteins 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, we revisited the Tom70 function, confirming that it supports the biogenesis of carriers and other mitochondrial proteins which considerably expands the set of Tom70-dependent mitochondrial proteins. However, the crucial activity of Tom70 is its recruitment of cytosolic chaperones to the outer membrane. Surprisingly, tethering an unrelated chaperone-binding domain onto the mitochondrial surface complements most of the defects caused by the absence of Tom70. In vivo, small single spanning inner membrane proteins can be particularly problematic when present in excess and the chaperone-binding ability of Tom70 is crucial to suppress their proteotoxicity. Thus, the predominant function of Tom70 is more that of a cytosolic co-chaperone, and its role as mitochondria-specifying receptor apparently is of less immediate relevance.

2021-03-29 | PXD021173 | Pride

The ER-SURF pathway uses ER-mitochondria contact sites for protein targeting to mitochondria

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The ER-SURF pathway uses ER-mitochondria contact sites for protein targeting to mitochondria - Data Set 2

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DNA-seq of mitochondrial DNA from mouse heart that is both heart SOD2 knockout and deficient for mitochondrial DNA repair

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Distinct types of intramitochondrial protein aggregates protect mitochondria against proteotoxic stress - Data Set1: HSP78 AP-MS

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Mitoribosome profiling (MitoRiboSeq) data from HEK WT and mtRF1 knockout cell lines

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