Mitochondrial protein import: Two membranes, three translocases

Current Opinion in Cell Biology

Volumn 14, Issue 4, 2002, Pages 400-411

  Pfanner, Nikolaus ^a   Wiedemann, Nils ^a  

^a UNIVERSITY OF FREIBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CARRIER PROTEIN; MITOCHONDRIAL PROTEIN; PROTEIN PRECURSOR; PROTEIN TOM; UNCLASSIFIED DRUG; MOLECULAR MOTOR;

CHROMOSOME TRANSLOCATION; CYTOSOL; MEMBRANE; MITOCHONDRION; OUTER MEMBRANE; PRIORITY JOURNAL; REVIEW; ANIMAL; BIOLOGICAL MODEL; CELL NUCLEUS; ENZYMOLOGY; HUMAN; INTRACELLULAR MEMBRANE; METABOLISM; PROTEIN TRANSPORT;

ANIMALS; CELL NUCLEUS; CYTOSOL; HUMANS; INTRACELLULAR MEMBRANES; MEMBRANE TRANSPORT PROTEINS; MITOCHONDRIA; MITOCHONDRIAL PROTEINS; MODELS, BIOLOGICAL; MOLECULAR MOTOR PROTEINS; PROTEIN PRECURSORS; PROTEIN TRANSPORT;

EID: 0036702195     PISSN: 09550674     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0955-0674(02)00355-1     Document Type: Review

References (79)

1. Schatz G., Dobberstein B. Common principles of protein translocation across membranes. Science. 271:1996;1519-1526.
2. Bauer M.F., Hofmann S., Neupert W., Brunner M. Protein translocation into mitochondria: the role of TIM complexes. Trends Cell Biol. 10:2000;25-31.
3. Jensen R.E., Johnson A.E. Opening the door to mitochondrial protein import. Nat Struct Biol. 8:2001;1008-1010.
4. Pfanner N., Geissler A. Versatility of the mitochondrial protein import machinery. Nat Rev Mol Cell Biol. 2:2001;339-349.
5. Brix J., Dietmeier K., Pfanner N. Differential recognition of preproteins by the purified cytosolic domains of the mitochondrial import receptors Tom20, Tom22, and Tom70. J Biol Chem. 272:1997;20730-20735.
6. Meisinger C., Ryan M.T., Hill K., Model K., Lim J.H., Sickmann A., Müller H., Meyer H.E., Wagner R., Pfanner N. 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. Mol Cell Biol. 21:2001;2337-2348.
7. Abe Y., Shodai T., Muto T., Mihara K., Torii H., Nishikawa S., Endo T., Kohda D. Structural basis of presequence recognition by the mitochondrial protein import receptor Tom20. Cell. 100:2000;551-560. Tom20 is the main receptor for preproteins with cleavable presequences. The NMR structure of the cytosolic domain of Tom20 in complex with a presequence reveals the mode of initial targeting to mitochondria. Tom20 possesses a hydrophobic groove that binds the hydrophobic side of the amphipathic α-helical presequence.
8. Wiedemann N., Pfanner N., Ryan M.T. The three modules of ADP/ATP carrier cooperate in receptor recruitment and translocation into mitochondria. EMBO J. 20:2001;951-960. The import of the ADP/ATP carrier is directed by internal targeting signals. Wiedemann et al. report that several targeting signals function simultaneously in import of the precursor protein such that several Tom70 molecules are recruited to one carrier molecule. The targeting signals cooperate also in the transfer of the precursor through the general import pore of the outer membrane. In contrast to presequence-containing preproteins that are translocated as linear polypeptide chain, the carrier precursor crosses the outer membrane in a loop formation.
9. Brix J., Rüdiger S., Bukau B., Schneider-Mergener J., Pfanner N. Distribution of binding sequences for the mitochondrial import receptors Tom20, Tom22, and Tom70 in a presequence-carrying preprotein and a non-cleavable preprotein. J Biol Chem. 274:1999;16522-16530.
10. Brix J., Ziegler G.A., Dietmeier K., Schneider-Mergener J., Schulz G.E., Pfanner N. The mitochondrial import receptor Tom70: identification of a 25 kDa core domain with a specific binding site for preproteins. J Mol Biol. 303:2000;479-488.
11. Hill K., Model K., Ryan M.T., Dietmeier K., Martin F., Wagner R., Pfanner N. Tom40 forms the hydrophilic channel of the mitochondrial import pore for preproteins. Nature. 395:1998;516-521.
12. Künkele K.P., Heins S., Dembowski M., Nargang F.E., Benz R., Thieffry M., Walz J., Lill R., Nussberger S., Neupert W. The preprotein translocation channel of the outer membrane of mitochondria. Cell. 93:1998;1009-1019.
13. Schwartz M.P., Matouschek A. The dimensions of the protein import channels in the outer and inner mitochondrial membranes. ProcNatl Acad Sci USA. 96:1999;13086-13090.
14. Ahting U., Thieffry M., Engelhardt H., Hegerl R., Neupert W., Nussberger S. Tom40, the pore-forming component of the protein-conducting TOM channel in the outer membrane of mitochondria. J Cell Biol. 153:2001;1151-1160.
15. Dekker P.J., Ryan M.T., Brix J., Müller H., Hönlinger A., Pfanner N. Preprotein translocase of the outer mitochondrial membrane: molecular dissection and assembly of the general import pore complex. Mol Cell Biol. 18:1998;6515-6524.
16. Stan T., Ahting U., Dembowski M., Künkele K.P., Nussberger S., Neupert W., Rapaport D. Recognition of preproteins by the isolated TOM complex of mitochondria. EMBO J. 19:2000;4895-4902. Stan et al. isolated the TOM complex to perform mitochondria-free import experiments. Chemical amounts of a mitochondrial preprotein were shown to bind to the holo complex and even to the trypsinised core complex (where the receptor domains were removed by treatment with trypsin). The authors determined that the binding affinity of the precursor to the core complex was significantly higher than to individual Tom proteins, indicating the presence of several binding sites in the complex. The purified TOM complex mediated partial translocation of a preprotein.
17. van Wilpe S., Ryan M.T., Hill K., Maarse A.C., Meisinger C., Brix J., Dekker P.J., Moczko M., Wagner R., Meijer M., et al. Tom22 is a multifunctional organizer of the mitochondrial preprotein translocase. Nature. 401:1999;485-489.
18. Dietmeier K., Hönlinger A., Bömer U., Dekker P.J., Eckerskorn C., Lottspeich F., Kübrich M., Pfanner N. Tom5 functionally links mitochondrial preprotein receptors to the general import pore. Nature. 388:1997;195-200.
19. Kurz M., Martin H., Rassow J., Pfanner N., Ryan M.T. Biogenesis of Tim proteins of the mitochondrial carrier import pathway: differential targeting mechanisms and crossing over with the main import pathway. Mol Biol Cell. 10:1999;2461-2474.
20. Model K., Prinz T., Ruiz T., Radermacher M., Krimmer T., Kühlbrandt W., Pfanner N., Meisinger C. Protein translocase of the outer mitochondrial membrane: role of import receptors in the structural organization of the TOM complex. J Mol Biol. 316:2002;657-666.
21. Krimmer T., Rapaport D., Ryan M.T., Meisinger C., Kassenbrock C.K., Blachly-Dyson E., Forte M., Douglas M.G., Neupert W., Nargang F.E., et al. Biogenesis of porin of the outer mitochondrial membrane involves an import pathway via receptors and the general import pore of the TOM complex. J Cell Biol. 152:2001;289-300.
22. Stuart R.A., Nicholson D.W., Neupert W. Early steps in mitochondrial protein import: receptor functions can be substituted by the membrane insertion activity of apocytochrome c. Cell. 60:1990;31-43.
23. Diekert K., de Kroon A.I., Ahting U., Niggemeyer B., Neupert W., de Kruijff B., Lill R. Apocytochrome c requires the TOM complex for translocation across the mitochondrial outer membrane. EMBO J. 20:2001;5626-5635. Diekert et al. reconstituted the import of apocytochrome c using proteo-liposomes. The import of the precursor of cytochrome c strictly depended on the presence of the TOM complex, but even the trypsin-resistant core of the TOM complex was sufficient for its import. When the TOM complex was occupied with saturating amounts of a presequence-containing preprotein, the import of apocytochrome c was not inhibited. Apocytochrome c thus uses the same translocase complex as other preproteins, but the actual pathway through the translocase is different.
24. Schneider H., Söllner T., Dietmeier K., Eckerskorn C., Lottspeich F., Trülzsch B., Neupert W., Pfanner N. Targeting of the master receptor MOM19 to mitochondria. Science. 254:1991;1659-1662.
25. Keil P., Pfanner N. Insertion of MOM22 into the mitochondrial outer membrane strictly depends on surface receptors. FEBS Lett. 321:1993;197-200.
26. Keil P., Weinzierl A., Kiebler M., Dietmeier K., Söllner T., Pfanner N. Biogenesis of the mitochondrial receptor complex. Two receptors are required for binding of MOM38 to the outer membrane surface. J Biol Chem. 268:1993;19177-19180.
27. Model K., Meisinger C., Prinz T., Wiedemann N., Truscott K.N., Pfanner N., Ryan M.T. Multistep assembly of the protein import channel of the mitochondrial outer membrane. Nat Struct Biol. 8:2001;361-370. This study dissects the assembly pathway of the precursor of the channel protein Tom40 to its mature form in the 400 kDa TOM complex of the outer membrane, which involves the participation of every other TOM protein. The precursor of Tom40 is targeted by receptors to the TOM complex and, surprisingly, is translocated across the outer membrane to the intermembrane space side, where it forms an early assembly intermediate of 250 kDa. This complex disassembles to form a late assembly intermediate of 100 kDa that integrates into the outer membrane. Finally, the complex is converted to the mature 400 kDa complex. The mature complex shows a highly dynamic behaviour and continuously dissociates to the late assembly intermediate, followed by re-assembly.
28. Dembowski M., Künkele K.P., Nargang F.E., Neupert W., Rapaport D. Assembly of Tom6 and Tom7 into the TOM core complex of Neurospora crassa. J Biol Chem. 276:2001;17679-17685.
29. Rapaport D., Neupert W. Biogenesis of Tom40, core component of the TOM complex of mitochondria. J Cell Biol. 146:1999;321-331.
30. Hönlinger A., Bömer U., Alconada A., Eckerskorn C., Lottspeich F., Dietmeier K., Pfanner N. Tom7 modulates the dynamics of the mitochondrial outer membrane translocase and plays a pathway-related role in protein import. EMBO J. 15:1996;2125-2137.
31. Rapaport D., Taylor R.D., Käser M., Langer T., Neupert W., Nargang F.E. Structural requirements of Tom40 for assembly into preexisting TOM complexes of mitochondria. Mol Biol Cell. 12:2001;1189-1198.
32. Bauer M.F., Sirrenberg C., Neupert W., Brunner M. Role of Tim23 as voltage sensor and presequence receptor in protein import into mitochondria. Cell. 87:1996;33-41.
33. Komiya T., Rospert S., Koehler C., Looser R., Schatz G., Mihara K. Interaction of mitochondrial targeting signals with acidic receptor domains along the protein import pathway: evidence for the 'acid chain' hypothesis. EMBO J. 17:1998;3886-3898.
34. Truscott K.N., Kovermann P., Geissler A., Merlin A., Meijer M., Driessen A.J., Rassow J., Pfanner N., Wagner R. A presequence- and voltage-sensitive channel of the mitochondrial preprotein translocase formed by Tim23. Nat Struct Biol. 8:2001;1074-1082. The presequence translocase of the mitochondrial inner membrane is a multiprotein complex. Tim23 alone forms a cation-selective channel activated by the membrane potential and positively charged presequences. The carboxy-terminal membrane-integrated domain of Tim23 forms the channel that is large enough to translocate a linear polypeptide chain, whereas the amino-terminal domain is required for selectivity and high affinity presequence interaction.
35. Lohret T.A., Jensen R.E., Kinnally K.W. Tim23, a protein import component of the mitochondrial inner membrane, is required for normal activity of the multiple conductance channel, MCC. J Cell Biol. 137:1997;377-386.
36. Dekker P.J., Martin F., Maarse A.C., Bömer U., Müller H., Guiard B., Meijer M., Rassow J., Pfanner N. The Tim core complex defines the number of mitochondrial translocation contact sites and can hold arrested preproteins in the absence of matrix Hsp70-Tim44. EMBO J. 16:1997;5408-5419.
37. Ryan K.R., Leung R.S., Jensen R.E. Characterization of the mitochondrial inner membrane translocase complex: the Tim23p hydrophobic domain interacts with Tim17p but not with other Tim23p molecules. Mol Cell Biol. 18:1998;178-187.
38. Milisav I., Moro F., Neupert W., Brunner M. Modular structure of the TIM23 preprotein translocase of mitochondria. J Biol Chem. 276:2001;25856-25861.
39. Donzeau M., Kaldi K., Adam A., Paschen S., Wanner G., Guiard B., Bauer M.F., Neupert W., Brunner M. Tim23 links the inner and outer mitochondrial membranes. Cell. 101:2000;401-412. Donzeau et al. reinvestigated the topology of the integral inner membrane protein Tim23. Using protease treatment and fusion protein experiments combined with immunolabeling of mitochondria, the authors concluded that the amino terminus of Tim23 spans the outer membrane. Tim23 is therefore proposed to span two membranes. This observation may be important for protein translocation; however, no association between Tim23 and the TOM complex was found by the authors.
40. Martin J., Mahlke K., Pfanner N. Role of an energized inner membrane in mitochondrial protein import. (( drives the movement of presequences. J Biol Chem. 266:1991;18051-18057.
41. Strub A., Röttgers K., Voos W. The Hsp70 peptide-binding domain determines the interaction of the ATPase domain with Tim44 in mitochondria. EMBO J. 21:2002;2626-2635.
42. Moro F., Okamoto K., Donzeau M., Neupert W., Brunner M. Mitochondrial protein import: molecular basis of the ATP-dependent interaction of MtHsp70 with Tim44. J Biol Chem. 277:2002;6874-6880.
43. Kang P.J., Ostermann J., Shilling J., Neupert W., Craig E.A., Pfanner N. Requirement for Hsp70 in the mitochondrial matrix for translocation and folding of precursor proteins. Nature. 348:1990;137-143.
44. Gaume B., Klaus C., Ungermann C., Guiard B., Neupert W., Brunner M. Unfolding of preproteins upon import into mitochondria. EMBO J. 17:1998;6497-6507.
45. Glick B.S. Can Hsp70 proteins act as force-generating motors? Cell. 80:1995;11-14.
46. Voos W., von Ahsen O., Müller H., Guiard B., Rassow J., Pfanner N. Differential requirement for the mitochondrial Hsp70-Tim44 complex in unfolding and translocation of preproteins. EMBO J. 15:1996;2668-2677.
47. Matouschek A., Azem A., Ratliff K., Glick B.S., Schmid K., Schatz G. Active unfolding of precursor proteins during mitochondrial protein import. EMBO J. 16:1997;6727-6736.
48. Voisine C., Craig E.A., Zufall N., von Ahsen O., Pfanner N., Voos W. The protein import motor of mitochondria: unfolding and trapping of preproteins are distinct and separable functions of matrix Hsp70. Cell. 97:1999;565-574.
49. Geissler A., Rassow J., Pfanner N., Voos W. Mitochondrial import driving forces: enhanced trapping by matrix Hsp70 stimulates translocation and reduces the membrane potential dependence of loosely folded preproteins. Mol Cell Biol. 21:2001;7097-7104. Two models for the role of mitochondrial heat shock protein 70 (mtHsp70) in the translocation of preproteins into the matrix are discussed: active pulling by mtHsp70 or passive binding (trapping) of the preprotein. This is the first report directly demonstrating that trapping is one of the molecular mechanisms of mtHsp70. The study used a mutant form of mtHsp70 with an enhanced trapping of preproteins. Import of a loosely folded preprotein at a low inner membrane potential was more efficient in the mutant mitochondria compared to wild-type mitochondria. However, the study also demonstrated that trapping alone is not sufficient for import of a folded preprotein, indicating that both mechanisms, trapping and pulling, cooperate in import of mitochondrial preproteins.
50. Lim J.H., Martin F., Guiard B., Pfanner N., Voos W. The mitochondrial Hsp70-dependent import system actively unfolds preproteins and shortens the lag phase of translocation. EMBO J. 20:2001;941-950.
51. Huang S., Ratliff K.S., Schwartz M.P., Spenner J.M., Matouschek A. Mitochondria unfold precursor proteins by unraveling them from their N-termini. Nat Struct Biol. 6:1999;1132-1138.
52. Huang S., Ratliff K.S., Matouschek A. Protein unfolding by the mitochondrial membrane potential. Nat Struct Biol. 9:2002;301-307. Huang et al. studied the mitochondrial import of a fusion protein consisting of a folded domain and a loosely folded amino-terminal pre-sequence of different length. The import of a short preprotein was slow since it depended on spontaneous unfolding of the folded domain, whereas the unfolding of a long preprotein was catalysed by the ATP-driven mitochondrial import motor, mtHsp70, when the loosely folded presequence was long enough to reach into the matrix (and thus import was rapid). Unexpectedly, the unfolding of a preprotein of intermediate length depended on the magnitude of the membrane potential across the inner membrane. In this case, the loosely folded presequence was just long enough to reach to the inner membrane and respond to the electric field of the membrane potential. This suggests that the electrophoretic effect of the membrane potential exerted a pulling force on the positively charged presequence and thereby promoted active unfolding of the preprotein.
53. Gavel Y., von Heijne G. Cleavage-site motifs in mitochondrial targeting peptides. Protein Eng. 4:1990;33-37.
54. Taylor A.B., Smith B.S., Kitada S., Kojima K., Miyaura H., Otwinowski Z., Ito A., Deisenhofer J. Crystal structures of mitochondrial processing peptidase reveal the mode for specific cleavage of import signal sequences. Structure. 9:2001;615-625. The crystal structure of the mitochondrial processing peptidase (MPP) with bound presequence peptides has important implications for the import of cleavable preproteins. MPP binds the presequences in an extended conformation, whereas the receptor Tom20 has been shown to bind presequences in α-helical conformation (see Abe et al. 2000 [7••] ). Therefore, the conformation of presequences changes during the import process in a context-dependent manner. Moreover the structure of MPP provides a molecular understanding of how this peptidase specifically recognises and cleaves mitochondrial preproteins.
55. Hönlinger A., Kübrich M., Moczko M., Gärtner F., Mallet L., Bussereau F., Eckerskorn C., Lottspeich F., Dietmeier K., Jacquet M., et al. The mitochondrial receptor complex: Mom22 is essential for cell viability and directly interacts with preproteins. Mol Cell Biol. 15:1995;3382-3389.
56. Schatz G. Just follow the acid chain. Nature. 388:1997;121-122.
57. Gordon D.M., Wang J., Amutha B., Pain D. Self-association and precursor protein binding of Saccharomyces cerevisiae Tom40p, the core component of the protein translocation channel of the mitochondrial outer membrane. Biochem J. 356:2001;207-215.
58. Pfanner N., Tropschug M., Neupert W. Mitochondrial protein import: nucleoside triphosphates are involved in conferring import-competence to precursors. Cell. 49:1987;815-823.
59. Ryan M.T., Müller H., Pfanner N. Functional staging of ADP/ATP carrier translocation across the outer mitochondrial membrane. J Biol Chem. 274:1999;20619-20627.
60. Luciano P., Vial S., Vergnolle M.A., Dyall S.D., Robinson D.R., Tokatlidis K. Functional reconstitution of the import of the yeast ADP/ATP carrier mediated by the TIM10 complex. EMBO J. 20:2001;4099-4106.
61. Curran S.P., Leuenberger D., Oppliger W., Koehler C.M. The Tim9p-Tim10p complex binds to the transmembrane domains of the ADP/ATP carrier. EMBO J. 21:2002;942-953. The Tim9-Tim10 complex of the mitochondrial intermembrane space is essential for the import of hydrophobic inner membrane proteins such as the metabolite carriers. The purified Tim9-Tim10 complex bound preferentially to several hydrophobic transmembrane regions of the ADP/ATP carrier (in peptide scan binding experiments). This supports the proposed role of the Tim9-Tim10 complex as a chaperone of the intermembrane space.
62. Koehler C.M., Jarosch E., Tokatlidis K., Schmid K., Schweyen R.J., Schatz G. Import of mitochondrial carriers mediated by essential proteins of the intermembrane space. Science. 279:1998;369-373.
63. Sirrenberg C., Endres M., Fölsch H., Stuart R.A., Neupert W., Brunner M. Carrier protein import into mitochondria mediated by the intermembrane proteins Tim10/Mrs11 and Tim12/Mrs5. Nature. 391:1998;912-915.
64. Koehler C.M., Merchant S., Oppliger W., Schmid K., Jarosch E., Dolfini L., Junne T., Schatz G., Tokatlidis K. Tim9p, an essential partner subunit of Tim10p for the import of mitochondrial carrier proteins. EMBO J. 17:1998;6477-6486.
65. Adam A., Endres M., Sirrenberg C., Lottspeich F., Neupert W., Brunner M. Tim9, a new component of the TIM22.54 translocase in mitochondria. EMBO J. 18:1999;313-319.
66. Murphy M.P., Leuenberger D., Curran S.P., Oppliger W., Koehler C.M. The essential function of the small Tim proteins in the TIM22 import pathway does not depend on formation of the soluble 70-kilodalton complex. Mol Cell Biol. 21:2001;6132-6138.
67. Sirrenberg C., Bauer M.F., Guiard B., Neupert W., Brunner M. Import of carrier proteins into the mitochondrial inner membrane mediated by Tim22. Nature. 384:1996;582-585.
68. Kerscher O., Holder J., Srinivasan M., Leung R.S., Jensen R.E. The Tim54p-Tim22p complex mediates insertion of proteins into the mitochondrial inner membrane. J Cell Biol. 139:1997;1663-1675.
69. Kerscher O., Sepuri N.B., Jensen R.E. Tim18p is a new component of the Tim54p-Tim22p translocon in the mitochondrial inner membrane. Mol Biol Cell. 11:2000;103-116.
70. Koehler C.M., Murphy M.P., Bally N.A., Leuenberger D., Oppliger W., Dolfini L., Junne T., Schatz G., Or E. Tim18p, a new subunit of the TIM22 complex that mediates insertion of imported proteins into the yeast mitochondrial inner membrane. Mol Cell Biol. 20:2000;1187-1193.
71. Kovermann P., Truscott K.N., Guiard B., Rehling P., Sepuri N.B., Müller H., Jensen R.E., Wagner R., Pfanner N. Tim22, the essential core of the mitochondrial protein insertion complex, forms a voltage-activated and signal-gated channel. Mol Cell. 9:2002;363-373. Kovermann et al. report that Tim22 is the only essential membrane-integrated subunit of the protein insertion complex for hydrophobic proteins of the inner mitochondrial membrane. Surprisingly, reconstituted Tim22 forms a hydrophilic channel that is just wide enough to accommodate two closely packed α helices such that the precursor of an inner membrane protein could insert in a loop formation. The channel is strongly activated only in the presence of both a high membrane potential and a specific targeting signal, demonstrating how the inner membrane barrier is kept tight in the absence of a targeting signal.
72. Wachter C., Schatz G., Glick B.S. Role of ATP in the intramitochondrial sorting of cytochrome c1 and the adenine nucleotide translocator. EMBO J. 11:1992;4787-4794.
73. Endres M., Neupert W., Brunner M. Transport of the ADP/ATP carrier of mitochondria from the TOM complex to the TIM22.54 complex. EMBO J. 18:1999;3214-3221.
74. Davis A.J., Sepuri N.B., Holder J., Johnson A.E., Jensen R.E. Two intermembrane space TIM complexes interact with different domains of Tim23p during its import into mitochondria. J Cell Biol. 150:2000;1271-1282. The Tim8-Tim13 complex selectively binds to the hydrophilic amino-terminal domain of the precursor of Tim23, whereas the Tim9-Tim10 complex binds to the carboxy-terminal hydrophobic domain of the Tim23 translocation intermediate. The positively charged amino acid residues in the matrix loops of the Tim23 precursor are essential for binding to the protein insertion complex, but are not important for the interaction with the Tim9-Tim10 complex.
75. Paschen S.A., Rothbauer U., Kaldi K., Bauer M.F., Neupert W., Brunner M. The role of the TIM8-13 complex in the import of Tim23 into mitochondria. EMBO J. 19:2000;6392-6400. The Tim8-Tim13 complex, which is not essential for cell viability in contrast to the Tim9-Tim10 complex, binds specifically to the import intermediate of the Tim23 precursor, although the overall import of Tim23 is only slightly reduced in yeast mitochondria lacking the Tim8-Tim13 complex. In the absence of a membrane potential, however, the Tim8-Tim13 complex discloses its function as a trans binding site (trap) for the precursor of Tim23 in the intermembrane space.
76. Hell K., Neupert W., Stuart R.A. Oxa1p acts as a general membrane insertion machinery for proteins encoded by mitochondrial DNA. EMBO J. 20:2001;1281-1288.
77. Preuss M., Leonhard K., Hell K., Stuart R.A., Neupert W., Herrmann J.M. Mba1, a novel component of the mitochondrial protein export machinery of the yeast Saccharomyces cerevisiae. J Cell Biol. 153:2001;1085-1095.
78. Broadley S.A., Demlow C.M., Fox T.D. Peripheral mitochondrial inner membrane protein, Mss2p, required for export of the mitochondrially coded Cox2p C tail in Saccharomyces cerevisiae. Mol Cell Biol. 21:2001;7663-7672.
79. Ahting U., Thun C., Hegerl R., Typke D., Nargang F.E., Neupert W., Nussberger S. The TOM core complex: the general protein import pore of the outer membrane of mitochondria. J Cell Biol. 147:1999;959-968.