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Vol. 20, Issue 10, 2530-2539, May 15, 2009

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Identification of the Signal Directing Tim9 and Tim10 into the Intermembrane Space of Mitochondria

Dusanka Milenkovic^*, Thomas Ramming^*, Judith M. Müller^*, Lena-Sophie Wenz^*, Natalia Gebert^*, Agnes Schulze-Specking^*, Diana Stojanovski^*, Sabine Rospert^*,, and Agnieszka Chacinska^*,

*Institut für Biochemie und Molekularbiologie, ZBMZ and Centre for Biological Signalling Studies (BIOSS), Universität Freiburg, 79104 Freiburg, Germany

Submitted November 12, 2008; Revised February 6, 2009; Accepted March 11, 2009
Monitoring Editor: Benjamin S. Glick

The intermembrane space of mitochondria contains the specific mitochondrial intermembrane space assembly (MIA) machinery that operates in the biogenesis pathway of precursor proteins destined to this compartment. The Mia40 component of the MIA pathway functions as a receptor and binds incoming precursors, forming an essential early intermediate in the biogenesis of intermembrane space proteins. The elements that are crucial for the association of the intermembrane space precursors with Mia40 have not been determined. In this study, we found that a region within the Tim9 and Tim10 precursors, consisting of only nine amino acid residues, functions as a signal for the engagement of substrate proteins with the Mia40 receptor. Furthermore, the signal contains sufficient information to facilitate the transfer of proteins across the outer membrane to the intermembrane space. Thus, here we have identified the mitochondrial intermembrane space sorting signal required for delivery of proteins to the mitochondrial intermembrane space.

Address correspondence to: Agnieszka Chacinska (agnieszka.chacinska{at}biochemie.uni-freiburg.de)

Abbreviations used: IMS, intermembrane space; MIA, mitochondrial intermembrane space import and assembly; MISS, mitochondrial intermembrane space sorting; PAGE, polyacrylamide gel electrophoresis; TIM, translocase of inner membrane; TOM, translocase of outer membrane.

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