QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 19, Issue 1, 226-236, January 2008

This Article Full Text Full Text (PDF) All Versions of this Article: E07-08-0814v1 19/1/226    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Müller, J. M. Articles by Chacinska, A. Search for Related Content PubMed PubMed Citation Articles by Müller, J. M. Articles by Chacinska, A.

Precursor Oxidation by Mia40 and Erv1 Promotes Vectorial Transport of Proteins into the Mitochondrial Intermembrane Space

Judith M. Müller^*, Dusanka Milenkovic^*, Bernard Guiard, Nikolaus Pfanner^*, and Agnieszka Chacinska^*

*Institut für Biochemie und Molekularbiologie, Zentrum für Biochemie und Molekulare Zellforschung, Universität Freiburg, D-79104 Freiburg, Germany; and Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, F-91190 Gif-sur-Yvette, France

Submitted August 22, 2007; Revised October 15, 2007; Accepted October 19, 2007
Monitoring Editor: Donald Newmeyer

The mitochondrial intermembrane space contains chaperone complexes that guide hydrophobic precursor proteins through this aqueous compartment. The chaperones consist of hetero-oligomeric complexes of small Tim proteins with conserved cysteine residues. The precursors of small Tim proteins are synthesized in the cytosol. Import of the precursors requires the essential intermembrane space proteins Mia40 and Erv1 that were proposed to form a relay for disulfide formation in the precursor proteins. However, experimental evidence for a role of Mia40 and Erv1 in the oxidation of intermembrane space precursors has been lacking. We have established a system to directly monitor the oxidation of precursors during import into mitochondria and dissected distinct steps of the import process. Reduced precursors bind to Mia40 during translocation into mitochondria. Both Mia40 and Erv1 are required for formation of oxidized monomers of the precursors that subsequently assemble into oligomeric complexes. Whereas the reduced precursors can diffuse back into the cytosol, the oxidized precursors are retained in the intermembrane space. Thus, oxidation driven by Mia40 and Erv1 determines vectorial transport of the precursors into the mitochondrial intermembrane space.

Address correspondence to: Nikolaus Pfanner (nikolaus.pfanner{at}biochemie.uni-freiburg.de)

Abbreviations used: AMS, 4-aceto-4'-maleimidylstilbene-2,2'-disulfonic acid; DTT, dithiothreitol; IA, iodoacetamide; IMS, intermembrane space; MIA, mitochondrial intermembrane space import and assembly; SAM, sorting and assembly machinery; TIM, translocase of inner membrane; TOM, translocase of outer membrane.

This article has been cited by other articles:

				D. Milenkovic, T. Ramming, J. M. Muller, L.-S. Wenz, N. Gebert, A. Schulze-Specking, D. Stojanovski, S. Rospert, and A. Chacinska Identification of the Signal Directing Tim9 and Tim10 into the Intermembrane Space of Mitochondria Mol. Biol. Cell, May 15, 2009; 20(10): 2530 - 2539. [Abstract] [Full Text] [PDF]

				B. Morgan, S. K. Ang, G. Yan, and H. Lu Zinc Can Play Chaperone-like and Inhibitor Roles during Import of Mitochondrial Small Tim Proteins J. Biol. Chem., March 13, 2009; 284(11): 6818 - 6825. [Abstract] [Full Text] [PDF]

				N. Terziyska, B. Grumbt, C. Kozany, and K. Hell Structural and Functional Roles of the Conserved Cysteine Residues of the Redox-regulated Import Receptor Mia40 in the Intermembrane Space of Mitochondria J. Biol. Chem., January 16, 2009; 284(3): 1353 - 1363. [Abstract] [Full Text] [PDF]

				A. Chacinska, B. Guiard, J. M. Muller, A. Schulze-Specking, K. Gabriel, S. Kutik, and N. Pfanner Mitochondrial Biogenesis, Switching the Sorting Pathway of the Intermembrane Space Receptor Mia40 J. Biol. Chem., October 31, 2008; 283(44): 29723 - 29729. [Abstract] [Full Text] [PDF]

				D. Stojanovski, D. Milenkovic, J. M. Muller, K. Gabriel, A. Schulze-Specking, M. J. Baker, M. T. Ryan, B. Guiard, N. Pfanner, and A. Chacinska Mitochondrial protein import: precursor oxidation in a ternary complex with disulfide carrier and sulfhydryl oxidase J. Cell Biol., October 20, 2008; 183(2): 195 - 202. [Abstract] [Full Text] [PDF]

				E. Lionaki, C. de Marcos Lousa, C. Baud, M. Vougioukalaki, G. Panayotou, and K. Tokatlidis The Essential Function of Tim12 in Vivo Is Ensured by the Assembly Interactions of Its C-terminal Domain J. Biol. Chem., June 6, 2008; 283(23): 15747 - 15753. [Abstract] [Full Text] [PDF]