Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 16 January 1998:
Vol. 279. no. 5349, pp. 369 - 373
DOI: 10.1126/science.279.5349.369
Prev | Table of Contents | Next

Reports

Import of Mitochondrial Carriers Mediated by Essential Proteins of the Intermembrane Space

Carla M. Koehler, Ernst Jarosch, Kostas Tokatlidis, Karl Schmid, Rudolf J. Schweyen, Gottfried Schatz *

In order to reach the inner membrane of the mitochondrion, multispanning carrier proteins must cross the aqueous intermembrane space. Two essential proteins of that space, Tim10p and Tim12p, were shown to mediate import of multispanning carriers into the inner membrane. Both proteins formed a complex with the inner membrane protein Tim22p. Tim10p readily dissociated from the complex and was required to transport carrier precursors across the outer membrane; Tim12p was firmly bound to Tim22p and mediated the insertion of carriers into the inner membrane. Neither protein was required for protein import into the other mitochondrial compartments. Both proteins may function as intermembrane space chaperones for the highly insoluble carrier proteins.

C. M. Koehler, K. Tokatlidis, K. Schmid, G. Schatz, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
E. Jarosch and R. J. Schweyen, Institut für Mikrobiologie und Genetik, University of Vienna, A-1030 Vienna, Austria.
*   To whom correspondence should be addressed. E-mail: schatz{at}ubaclu.unibas.ch

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Assembly Pathway of the Mitochondrial Carrier Translocase Involves Four Preprotein Translocases.
K. Wagner, N. Gebert, B. Guiard, K. Brandner, K. N. Truscott, N. Wiedemann, N. Pfanner, and P. Rehling (2008)
Mol. Cell. Biol. 28, 4251-4260
   Abstract »    Full Text »    PDF »
The Essential Function of Tim12 in Vivo Is Ensured by the Assembly Interactions of Its C-terminal Domain.
E. Lionaki, C. de Marcos Lousa, C. Baud, M. Vougioukalaki, G. Panayotou, and K. Tokatlidis (2008)
J. Biol. Chem. 283, 15747-15753
   Abstract »    Full Text »    PDF »
Precursor Oxidation by Mia40 and Erv1 Promotes Vectorial Transport of Proteins into the Mitochondrial Intermembrane Space.
J. M. Muller, D. Milenkovic, B. Guiard, N. Pfanner, and A. Chacinska (2008)
Mol. Biol. Cell 19, 226-236
   Abstract »    Full Text »    PDF »
Biogenesis of yeast dicarboxylate carrier: the carrier signature facilitates translocation across the mitochondrial outer membrane.
V. Zara, A. Ferramosca, L. Capobianco, K. M. Baltz, O. Randel, J. Rassow, F. Palmieri, and P. Papatheodorou (2007)
J. Cell Sci. 120, 4099-4106
   Abstract »    Full Text »    PDF »
Tim54p connects inner membrane assembly and proteolytic pathways in the mitochondrion.
D. K. Hwang, S. M. Claypool, D. Leuenberger, H. L. Tienson, and C. M. Koehler (2007)
J. Cell Biol. 178, 1161-1175
   Abstract »    Full Text »    PDF »
Biogenesis of the Essential Tim9 Tim10 Chaperone Complex of Mitochondria: SITE-SPECIFIC RECOGNITION OF CYSTEINE RESIDUES BY THE INTERMEMBRANE SPACE RECEPTOR Mia40.
D. Milenkovic, K. Gabriel, B. Guiard, A. Schulze-Specking, N. Pfanner, and A. Chacinska (2007)
J. Biol. Chem. 282, 22472-22480
   Abstract »    Full Text »    PDF »
Conserved Motifs Reveal Details of Ancestry and Structure in the Small TIM Chaperones of the Mitochondrial Intermembrane Space.
I. E. Gentle, A. J. Perry, F. H. Alcock, V. A. Likic, P. Dolezal, E. T. Ng, A. W. Purcell, M. McConnville, T. Naderer, A.-L. Chanez, et al. (2007)
Mol. Biol. Evol. 24, 1149-1160
   Abstract »    Full Text »    PDF »
The Tim9p/10p and Tim8p/13p Complexes Bind to Specific Sites on Tim23p during Mitochondrial Protein Import.
A. J. Davis, N. N. Alder, R. E. Jensen, and A. E. Johnson (2007)
Mol. Biol. Cell 18, 475-486
   Abstract »    Full Text »    PDF »
Mitochondrial Transporters as Novel Targets for Intracellular Calcium Signaling.
J. Satrustegui, B. Pardo, and A. del Arco (2007)
Physiol Rev 87, 29-67
   Abstract »    Full Text »    PDF »
Mammalian Polynucleotide Phosphorylase Is an Intermembrane Space RNase That Maintains Mitochondrial Homeostasis.
H.-W. Chen, R. N. Rainey, C. E. Balatoni, D. W. Dawson, J. J. Troke, S. Wasiak, J. S. Hong, H. M. McBride, C. M. Koehler, M. A. Teitell, et al. (2006)
Mol. Cell. Biol. 26, 8475-8487
   Abstract »    Full Text »    PDF »
A New Function in Translocation for the Mitochondrial i-AAA Protease Yme1: Import of Polynucleotide Phosphorylase into the Intermembrane Space.
R. N. Rainey, J. D. Glavin, H.-W. Chen, S. W. French, M. A. Teitell, and C. M. Koehler (2006)
Mol. Cell. Biol. 26, 8488-8497
   Abstract »    Full Text »    PDF »
Characterization of Mmp37p, a Saccharomyces cerevisiae Mitochondrial Matrix Protein with a Role in Mitochondrial Protein Import.
M. R. Gallas, M. K. Dienhart, R. A. Stuart, and R. M. Long (2006)
Mol. Biol. Cell 17, 4051-4062
   Abstract »    Full Text »    PDF »
Dissection of the Mitochondrial Import and Assembly Pathway for Human Tom40.
A. D. Humphries, I. C. Streimann, D. Stojanovski, A. J. Johnston, M. Yano, N. J. Hoogenraad, and M. T. Ryan (2005)
J. Biol. Chem. 280, 11535-11543
   Abstract »    Full Text »    PDF »
Assembly of the TOB Complex of Mitochondria.
S. J. Habib, T. Waizenegger, M. Lech, W. Neupert, and D. Rapaport (2005)
J. Biol. Chem. 280, 6434-6440
   Abstract »    Full Text »    PDF »
The Carboxyl-terminal Third of the Dicarboxylate Carrier Is Crucial for Productive Association with the Inner Membrane Twin-pore Translocase.
K. Brandner, P. Rehling, and K. N. Truscott (2005)
J. Biol. Chem. 280, 6215-6221
   Abstract »    Full Text »    PDF »
A Homolog of Albino3/OxaI Is Essential for Thylakoid Biogenesis in the Cyanobacterium Synechocystis sp. PCC6803.
E. Spence, S. Bailey, A. Nenninger, S. G. Moller, and C. Robinson (2004)
J. Biol. Chem. 279, 55792-55800
   Abstract »    Full Text »    PDF »
Defective Mitochondrial Protein Translocation Precludes Normal Caenorhabditis elegans Development.
S. P. Curran, E. P. Leverich, C. M. Koehler, and P. L. Larsen (2004)
J. Biol. Chem. 279, 54655-54662
   Abstract »    Full Text »    PDF »
The Role of Hot13p and Redox Chemistry in the Mitochondrial TIM22 Import Pathway.
S. P. Curran, D. Leuenberger, E. P. Leverich, D. K. Hwang, K. N. Beverly, and C. M. Koehler (2004)
J. Biol. Chem. 279, 43744-43751
   Abstract »    Full Text »    PDF »
The calcium-binding aspartate/glutamate carriers, citrin and aralar1, are new substrates for the DDP1/TIMM8a-TIMM13 complex.
K. Roesch, P. J. Hynds, R. Varga, L. Tranebjaerg, and C. M. Koehler (2004)
Hum. Mol. Genet. 13, 2101-2111
   Abstract »    Full Text »    PDF »
A Mutation Inactivating the Mitochondrial Inner Membrane Folate Transporter Creates a Glycine Requirement for Survival of Chinese Hamster Cells.
E. A. McCarthy, S. A. Titus, S. M. Taylor, C. Jackson-Cook, and R. G. Moran (2004)
J. Biol. Chem. 279, 33829-33836
   Abstract »    Full Text »    PDF »
Biogenesis of the Protein Import Channel Tom40 of the Mitochondrial Outer Membrane: INTERMEMBRANE SPACE COMPONENTS ARE INVOLVED IN AN EARLY STAGE OF THE ASSEMBLY PATHWAY.
N. Wiedemann, K. N. Truscott, S. Pfannschmidt, B. Guiard, C. Meisinger, and N. Pfanner (2004)
J. Biol. Chem. 279, 18188-18194
   Abstract »    Full Text »    PDF »
The Structural Basis of the TIM10 Chaperone Assembly.
H. Lu, A. P. Golovanov, F. Alcock, J. G. Grossmann, S. Allen, L.-Y. Lian, and K. Tokatlidis (2004)
J. Biol. Chem. 279, 18959-18966
   Abstract »    Full Text »    PDF »
Organization and Function of the Small Tim Complexes Acting along the Import Pathway of Metabolite Carriers into Mammalian Mitochondria.
N. Muhlenbein, S. Hofmann, U. Rothbauer, and M. F. Bauer (2004)
J. Biol. Chem. 279, 13540-13546
   Abstract »    Full Text »    PDF »
The Tim8-Tim13 Complex of Neurospora crassa Functions in the Assembly of Proteins into Both Mitochondrial Membranes.
S. C. Hoppins and F. E. Nargang (2004)
J. Biol. Chem. 279, 12396-12405
   Abstract »    Full Text »    PDF »
Reconstituted TOM Core Complex and Tim9/Tim10 Complex of Mitochondria Are Sufficient for Translocation of the ADP/ATP Carrier across Membranes.
A. Vasiljev, U. Ahting, F. E. Nargang, N. E. Go, S. J. Habib, C. Kozany, V. Panneels, I. Sinning, H. Prokisch, W. Neupert, et al. (2004)
Mol. Biol. Cell 15, 1445-1458
   Abstract »    Full Text »    PDF »
Mitochondria Use Different Mechanisms for Transport of Multispanning Membrane Proteins through the Intermembrane Space.
A. E. Frazier, A. Chacinska, K. N. Truscott, B. Guiard, N. Pfanner, and P. Rehling (2003)
Mol. Cell. Biol. 23, 7818-7828
   Abstract »    Full Text »    PDF »
Juxtaposition of the Two Distal CX3C Motifs via Intrachain Disulfide Bonding Is Essential for the Folding of Tim10.
S. Allen, H. Lu, D. Thornton, and K. Tokatlidis (2003)
J. Biol. Chem. 278, 38505-38513
   Abstract »    Full Text »    PDF »
Functional cooperation and separation of translocators in protein import into mitochondria, the double-membrane bounded organelles.
T. Endo, H. Yamamoto, and M. Esaki (2003)
J. Cell Sci. 116, 3259-3267
   Abstract »    Full Text »    PDF »
Trichomonas vaginalis Hmp35, a Putative Pore-forming Hydrogenosomal Membrane Protein, Can Form a Complex in Yeast Mitochondria.
S. D. Dyall, D. C. Lester, R. E. Schneider, M. G. Delgadillo-Correa, E. Plumper, A. Martinez, C. M. Koehler, and P. J. Johnson (2003)
J. Biol. Chem. 278, 30548-30561
   Abstract »    Full Text »    PDF »
The Dynamic Dimerization of the Yeast ADP/ATP Carrier in the Inner Mitochondrial Membrane Is Affected by Conserved Cysteine Residues.
S. D. Dyall, S. C. Agius, C. De Marcos Lousa, V. Trezeguet, and K. Tokatlidis (2003)
J. Biol. Chem. 278, 26757-26764
   Abstract »    Full Text »    PDF »
Trypanosoma brucei Cytochrome c1 Is Imported into Mitochondria Along an Unusual Pathway.
J. W. Priest and S. L. Hajduk (2003)
J. Biol. Chem. 278, 15084-15094
   Abstract »    Full Text »    PDF »
Protein Insertion into the Mitochondrial Inner Membrane by a Twin-Pore Translocase.
P. Rehling, K. Model, K. Brandner, P. Kovermann, A. Sickmann, H. E. Meyer, W. Kuhlbrandt, R. Wagner, K. N. Truscott, and N. Pfanner (2003)
Science 299, 1747-1751
   Abstract »    Full Text »    PDF »
Genomic and Proteomic Analysis of Mitochondrial Carrier Proteins in Arabidopsis.
A. H. Millar and J. L. Heazlewood (2003)
Plant Physiology 131, 443-453
   Abstract »    Full Text »    PDF »
Mitochondrial Import of the ADP/ATP Carrier: the Essential TIM Complex of the Intermembrane Space Is Required for Precursor Release from the TOM Complex.
K. N. Truscott, N. Wiedemann, P. Rehling, H. Muller, C. Meisinger, N. Pfanner, and B. Guiard (2002)
Mol. Cell. Biol. 22, 7780-7789
   Abstract »    Full Text »    PDF »
Assembly of Tim9 and Tim10 into a Functional Chaperone.
S. Vial, H. Lu, S. Allen, P. Savory, D. Thornton, J. Sheehan, and K. Tokatlidis (2002)
J. Biol. Chem. 277, 36100-36108
   Abstract »    Full Text »    PDF »
The role of the Tim8p-Tim13p complex in a conserved import pathway for mitochondrial polytopic inner membrane proteins.
S. P. Curran, D. Leuenberger, E. Schmidt, and C. M. Koehler (2002)
J. Cell Biol. 158, 1017-1027
   Abstract »    Full Text »    PDF »
The C66W Mutation in the Deafness Dystonia Peptide 1 (DDP1) Affects the Formation of Functional DDP1{middle dot}TIM13 Complexes in the Mitochondrial Intermembrane Space.
S. Hofmann, U. Rothbauer, N. Muhlenbein, W. Neupert, K.-D. Gerbitz, M. Brunner, and M. F. Bauer (2002)
J. Biol. Chem. 277, 23287-23293
   Abstract »    Full Text »    PDF »
The genetics of primary dystonias and related disorders.
A. H. Nemeth (2002)
Brain 125, 695-721
   Abstract »    Full Text »    PDF »
Human deafness dystonia syndrome is caused by a defect in assembly of the DDP1/TIMM8a-TIMM13 complex.
K. Roesch, S. P. Curran, L. Tranebjaerg, and C. M. Koehler (2002)
Hum. Mol. Genet. 11, 477-486
   Abstract »    Full Text »    PDF »
The Essential Function of the Small Tim Proteins in the TIM22 Import Pathway Does Not Depend on Formation of the Soluble 70-Kilodalton Complex.
M. P. Murphy, D. Leuenberger, S. P. Curran, W. Oppliger, and C. M. Koehler (2001)
Mol. Cell. Biol. 21, 6132-6138
   Abstract »    Full Text »    PDF »
Mitochondrial Mg2+ homeostasis is critical for group II intron splicing in vivo.
J. Gregan, M. Kolisek, and R. J. Schweyen (2001)
Genes & Dev. 15, 2229-2237
   Abstract »    Full Text »    PDF »
Mba1, a Novel Component of the Mitochondrial Protein Export Machinery of the Yeast Saccharomyces cerevisiae.
M. Preuss, K. Leonhard, K. Hell, R. A. Stuart, W. Neupert, and J. M. Herrmann (2001)
J. Cell Biol. 153, 1085-1096
   Abstract »    Full Text »    PDF »
Protein Import Channel of the Outer Mitochondrial Membrane: a Highly Stable Tom40-Tom22 Core Structure Differentially Interacts with Preproteins, Small Tom Proteins, and Import Receptors.
C. Meisinger, M. T. Ryan, K. Hill, K. Model, J. H. Lim, A. Sickmann, H. Müller, H. E. Meyer, R. Wagner, and N. Pfanner (2001)
Mol. Cell. Biol. 21, 2337-2348
   Abstract »    Full Text »
Two Intermembrane Space TIM Complexes Interact with Different Domains of Tim23p during Its Import into Mitochondria.
A. J. Davis, N. B. Sepuri, J. Holder, A. E. Johnson, and R. E. Jensen (2000)
J. Cell Biol. 150, 1271-1282
   Abstract »    Full Text »    PDF »
Presence of a Member of the Mitochondrial Carrier Family in Hydrogenosomes: Conservation of Membrane-Targeting Pathways between Hydrogenosomes and Mitochondria.
S. D. Dyall, C. M. Koehler, M. G. Delgadillo-Correa, P. J. Bradley, E. Plümper, D. Leuenberger, C. W. Turck, and P. J. Johnson (2000)
Mol. Cell. Biol. 20, 2488-2497
   Abstract »    Full Text »
Tim18p, a New Subunit of the TIM22 Complex That Mediates Insertion of Imported Proteins into the Yeast Mitochondrial Inner Membrane.
C. M. Koehler, M. P. Murphy, N. A. Bally, D. Leuenberger, W. Oppliger, L. Dolfini, T. Junne, G. Schatz, and E. Or (2000)
Mol. Cell. Biol. 20, 1187-1193
   Abstract »    Full Text »
The central matrix loop drives import of uncoupling protein 1 into mitochondria.
E Schleiff and H McBride (2000)
J. Cell Sci. 113, 2267-2272
   Abstract »    PDF »
Tim18p Is a New Component of the Tim54p-Tim22p Translocon in the Mitochondrial Inner Membrane.
O. Kerscher, N. B. Sepuri, and R. E. Jensen (2000)
Mol. Biol. Cell 11, 103-116
   Abstract »    Full Text »
Biogenesis of Mitochondrial Inner Membrane Proteins.
K. Tokatlidis and G. Schatz (1999)
J. Biol. Chem. 274, 35285-35288
   Full Text »    PDF »
The TOM Core Complex: The General Protein Import Pore of the Outer Membrane of Mitochondria.
U. Ahting, C. Thun, R. Hegerl, D. Typke, F. E. Nargang, W. Neupert, and S. Nussberger (1999)
J. Cell Biol. 147, 959-968
   Abstract »    Full Text »    PDF »
An internal targeting signal directing proteins into the mitochondrial intermembrane space.
K. Diekert, G. Kispal, B. Guiard, and R. Lill (1999)
PNAS 96, 11752-11757
   Abstract »    Full Text »    PDF »
Mutations Affecting a Yeast Mitochondrial Inner Membrane Protein, Pnt1p, Block Export of a Mitochondrially Synthesized Fusion Protein from the Matrix.
S. He and T. D. Fox (1999)
Mol. Cell. Biol. 19, 6598-6607
   Abstract »    Full Text »    PDF »
Functional Staging of ADP/ATP Carrier Translocation across the Outer Mitochondrial Membrane.
M. T. Ryan, H. Muller, and N. Pfanner (1999)
J. Biol. Chem. 274, 20619-20627
   Abstract »    Full Text »    PDF »
Biogenesis of Tim Proteins of the Mitochondrial Carrier Import Pathway: Differential Targeting Mechanisms and Crossing Over with the Main Import Pathway.
M. Kurz, H. Martin, J. Rassow, N. Pfanner, and M. T. Ryan (1999)
Mol. Biol. Cell 10, 2461-2474
   Abstract »    Full Text »
Mitochondria and dystonia: The movement disorder connection?.
D. C. Wallace and D. G. Murdock (1999)
PNAS 96, 1817-1819
   Full Text »    PDF »
Human deafness dystonia syndrome is a mitochondrial disease.
C. M. Koehler, D. Leuenberger, S. Merchant, A. Renold, T. Junne, and G. Schatz (1999)
PNAS 96, 2141-2146
   Abstract »    Full Text »    PDF »
Tim23p Contains Separate and Distinct Signals for Targeting to Mitochondria and Insertion into the Inner Membrane.
A. J. Davis, K. R. Ryan, and R. E. Jensen (1998)
Mol. Biol. Cell 9, 2577-2593
   Abstract »    Full Text »
The Import Route of ADP/ATP Carrier into Mitochondria Separates from the General Import Pathway of Cleavable Preproteins at the trans Side of the Outer Membrane.
M. Kubrich, J. Rassow, W. Voos, N. Pfanner, and A. Honlinger (1998)
J. Biol. Chem. 273, 16374-16381
   Abstract »    Full Text »    PDF »
Role of the Negative Charges in the Cytosolic Domain of TOM22 in the Import of Precursor Proteins into Mitochondria.
F. E. Nargang, D. Rapaport, R. G. Ritzel, W. Neupert, and R. Lill (1998)
Mol. Cell. Biol. 18, 3173-3181
   Abstract »    Full Text »
Identification of Mammalian TOM22 as a Subunit of the Preprotein Translocase of the Mitochondrial Outer Membrane.
K. Saeki, H. Suzuki, M. Tsuneoka, M. Maeda, R. Iwamoto, H. Hasuwa, S. Shida, T. Takahashi, M. Sakaguchi, T. Endo, et al. (2000)
J. Biol. Chem. 275, 31996-32002
   Abstract »    Full Text »    PDF »
Characterization of Rat TOM40, a Central Component of the Preprotein Translocase of the Mitochondrial Outer Membrane.
H. Suzuki, Y. Okazawa, T. Komiya, K. Saeki, E. Mekada, S. Kitada, A. Ito, and K. Mihara (2000)
J. Biol. Chem. 275, 37930-37936
   Abstract »    Full Text »    PDF »
Modular Structure of the TIM23 Preprotein Translocase of Mitochondria.
I. Milisav, F. Moro, W. Neupert, and M. Brunner (2001)
J. Biol. Chem. 276, 25856-25861
   Abstract »    Full Text »    PDF »
Role of the Deafness Dystonia Peptide 1 (DDP1) in Import of Human Tim23 into the Inner Membrane of Mitochondria.
U. Rothbauer, S. Hofmann, N. Muhlenbein, S. A. Paschen, K.-D. Gerbitz, W. Neupert, M. Brunner, and M. F. Bauer (2001)
J. Biol. Chem. 276, 37327-37334
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)