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Tom5 functionally links mitochondrial preprotein receptors to the general import pore

Abstract

Most mitochondrial proteins are synthesized as preproteins on cytosolic polysomes and are subsequently imported into the organelle1,2,3. The mitochondrial outer membrane contains a multisubunit preprotein translocase (Tom) which has receptors on the cytosolic side and a general import pore (GIP) in the membrane. Tom20–Tom22 and Tom70–Tom37 function as import receptors4,5,6,7 with a preference for preproteins that have amino-terminal presequences or internal targeting information, respectively. Tom40 is an essential constituent of the GIP8,9, whereas Tom6 and Tom7 modulate the assembly and dissociation of the Tom machinery10,11. Here we report the identification of Tom5, a small subunit that has a crucial role importing preproteins destined for all four mitochondrial subcompartments. Tom5 has a single membrane anchor and a cytosolic segment with a negative net charge, and accepts preproteins from the receptors and mediates their insertion into the GIP. We conclude that Tom5 represents a functional link between surface receptors and GIP, and is part of an ‘acid chain’5 that guides the stepwise transport of positively charged mitochondrial targeting sequences.

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Figure 1: Tom5 is an integral mitochondrial outer membrane protein exposed to the cytosol.
Figure 2: Tom5 is required for import of preproteins to all four mitochondrial subcompartments.
Figure 3: Crosslinking of preproteins to Tom5 depends on the import stage.
Figure 4: Tom5 functions between receptors and GIP.

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Acknowledgements

We thank M. Ryan for comments on the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 388 Freiburg, the Fonds der Chemischen Industrie (N.P.) and a long-term fellowship from the Human Frontier Science Program (P.J.T.D.).

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Correspondence to Nikolaus Pfanner.

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Dietmeier, K., Hönlinger, A., Bömer, U. et al. Tom5 functionally links mitochondrial preprotein receptors to the general import pore. Nature 388, 195–200 (1997). https://doi.org/10.1038/40663

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