Identification of the signal directing Tim9 and Tim10 into the intermembrane space of mitochondria

• Published in: Molecular biology of the cell Vol. 20; no. 10; pp. 2530 - 2539
• Main Authors: Milenkovic, Dusanka, Ramming, Thomas, Müller, Judith M, Wenz, Lena-Sophie, Gebert, Natalia, Schulze-Specking, Agnes, Stojanovski, Diana, Rospert, Sabine, Chacinska, Agnieszka
• Format: Journal Article
• Language: English
• Published: United States The American Society for Cell Biology 15.05.2009
• Subjects: Amino Acid Sequence; Leucine - metabolism; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Mitochondria - metabolism; Mitochondrial Membrane Transport Proteins - chemistry; Mitochondrial Membrane Transport Proteins - metabolism; Mitochondrial Membranes - metabolism; Molecular Sequence Data; Protein Binding; Protein Precursors - metabolism; Protein Sorting Signals; Protein Transport; Recombinant Fusion Proteins - metabolism; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - metabolism
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.E08-11-1108

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.