A discrete pathway for the transfer of intermembrane space proteins across the outer membrane of mitochondria.

Agnieszka Gornicka, Piotr Bragoszewski, Piotr Chroscicki, Lena-Sophie Wenz, Christian Schulz, Peter Rehling, Agnieszka Chacinska

Molecular biology of the cell 2014 Dec 15

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Mitochondrial proteins are synthesized on cytosolic ribosomes and imported into mitochondria with the help of protein translocases. For the majority of precursor proteins, the role of the translocase of the outer membrane (TOM) and mechanisms of their transport across the outer mitochondrial membrane are well recognized. However, little is known about the mode of membrane translocation for proteins that are targeted to the intermembrane space via the redox-driven mitochondrial intermembrane space import and assembly (MIA) pathway. On the basis of the results obtained from an in organello competition import assay, we hypothesized that MIA-dependent precursor proteins use an alternative pathway to cross the outer mitochondrial membrane. Here we demonstrate that this alternative pathway involves the protein channel formed by Tom40. We sought a translocation intermediate by expressing tagged versions of MIA-dependent proteins in vivo. We identified a transient interaction between our model substrates and Tom40. Of interest, outer membrane translocation did not directly involve other core components of the TOM complex, including Tom22. Thus MIA-dependent proteins take another route across the outer mitochondrial membrane that involves Tom40 in a form that is different from the canonical TOM complex. © 2014 Gornicka et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Citation

Agnieszka Gornicka, Piotr Bragoszewski, Piotr Chroscicki, Lena-Sophie Wenz, Christian Schulz, Peter Rehling, Agnieszka Chacinska. A discrete pathway for the transfer of intermembrane space proteins across the outer membrane of mitochondria. Molecular biology of the cell. 2014 Dec 15;25(25):3999-4009