Logo of embojLink to Publisher's site
EMBO J. 1999 Jun 15; 18(12): 3214–3221.
PMCID: PMC1171402

Transport of the ADP/ATP carrier of mitochondria from the TOM complex to the TIM22.54 complex.


Members of the mitochondrial carrier family such as the ADP/ATP carrier (AAC) are composed of three structurally related modules. Here we show that each of the modules contains a mitochondrial import signal recognized by Tim10 and Tim12 in the intermembrane space. The first and the second module are translocated across the outer membrane independently of the membrane potential, DeltaDeltapsipsi, but they are not inserted into the inner membrane. The third module interacts tightly with the TOM complex and thereby prevents complete translocation of the precursor across the outer membrane. At this stage, binding of a TIM9.10 complex confers a topology to the translocation intermediate which reflects the modular structure of the AAC. The precursor is then transferred to the TIM9.10.12 complex, still interacting with the TOM complex. Release of the precursor from the TOM complex and insertion into the inner membrane by the TIM22.54 complex requires a DeltaDeltapsipsi-responsive signal in the third module.

Full Text

The Full Text of this article is available as a PDF (223K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • 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. 1999 Jan 15;18(2):313–319. [PMC free article] [PubMed]
  • Azem A, Oppliger W, Lustig A, Jenö P, Feifel B, Schatz G, Horst M. The mitochondrial hsp70 chaperone system. Effect of adenine nucleotides, peptide substrate, and mGrpE on the oligomeric state of mhsp70. J Biol Chem. 1997 Aug 15;272(33):20901–20906. [PubMed]
  • Bauer MF, Sirrenberg C, Neupert W, Brunner M. Role of Tim23 as voltage sensor and presequence receptor in protein import into mitochondria. Cell. 1996 Oct 4;87(1):33–41. [PubMed]
  • Bömer U, Maarse AC, Martin F, Geissler A, Merlin A, Schönfisch B, Meijer M, Pfanner N, Rassow J. Separation of structural and dynamic functions of the mitochondrial translocase: Tim44 is crucial for the inner membrane import sites in translocation of tightly folded domains, but not of loosely folded preproteins. EMBO J. 1998 Aug 3;17(15):4226–4237. [PMC free article] [PubMed]
  • Dietmeier K, Hönlinger A, Bömer U, Dekker PJ, Eckerskorn C, Lottspeich F, Kübrich M, Pfanner N. Tom5 functionally links mitochondrial preprotein receptors to the general import pore. Nature. 1997 Jul 10;388(6638):195–200. [PubMed]
  • Emtage JL, Jensen RE. MAS6 encodes an essential inner membrane component of the yeast mitochondrial protein import pathway. J Cell Biol. 1993 Sep;122(5):1003–1012. [PMC free article] [PubMed]
  • Hill K, Model K, Ryan MT, Dietmeier K, Martin F, Wagner R, Pfanner N. Tom40 forms the hydrophilic channel of the mitochondrial import pore for preproteins [see comment]. Nature. 1998 Oct 1;395(6701):516–521. [PubMed]
  • Horst M, Hilfiker-Rothenfluh S, Oppliger W, Schatz G. Dynamic interaction of the protein translocation systems in the inner and outer membranes of yeast mitochondria. EMBO J. 1995 May 15;14(10):2293–2297. [PMC free article] [PubMed]
  • Horst M, Oppliger W, Rospert S, Schönfeld HJ, Schatz G, Azem A. Sequential action of two hsp70 complexes during protein import into mitochondria. EMBO J. 1997 Apr 15;16(8):1842–1849. [PMC free article] [PubMed]
  • Jarosch E, Tuller G, Daum G, Waldherr M, Voskova A, Schweyen RJ. Mrs5p, an essential protein of the mitochondrial intermembrane space, affects protein import into yeast mitochondria. J Biol Chem. 1996 Jul 19;271(29):17219–17225. [PubMed]
  • Jarosch E, Rödel G, Schweyen RJ. A soluble 12-kDa protein of the mitochondrial intermembrane space, Mrs11p, is essential for mitochondrial biogenesis and viability of yeast cells. Mol Gen Genet. 1997 Jun;255(2):157–165. [PubMed]
  • Kerscher O, Holder J, Srinivasan M, Leung RS, Jensen RE. The Tim54p-Tim22p complex mediates insertion of proteins into the mitochondrial inner membrane. J Cell Biol. 1997 Dec 29;139(7):1663–1675. [PMC free article] [PubMed]
  • Koehler CM, Jarosch E, Tokatlidis K, Schmid K, Schweyen RJ, Schatz G. Import of mitochondrial carriers mediated by essential proteins of the intermembrane space. Science. 1998 Jan 16;279(5349):369–373. [PubMed]
  • Koehler CM, 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. 1998 Nov 16;17(22):6477–6486. [PMC free article] [PubMed]
  • Kronidou NG, Oppliger W, Bolliger L, Hannavy K, Glick BS, Schatz G, Horst M. Dynamic interaction between Isp45 and mitochondrial hsp70 in the protein import system of the yeast mitochondrial inner membrane. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12818–12822. [PMC free article] [PubMed]
  • Kübrich M, Rassow J, Voos W, Pfanner N, Hönlinger A. 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. J Biol Chem. 1998 Jun 26;273(26):16374–16381. [PubMed]
  • Künkele KP, Heins S, Dembowski M, Nargang FE, Benz R, Thieffry M, Walz J, Lill R, Nussberger S, Neupert W. The preprotein translocation channel of the outer membrane of mitochondria. Cell. 1998 Jun 12;93(6):1009–1019. [PubMed]
  • Nelson DR, Felix CM, Swanson JM. Highly conserved charge-pair networks in the mitochondrial carrier family. J Mol Biol. 1998 Mar 27;277(2):285–308. [PubMed]
  • Neupert W. Protein import into mitochondria. Annu Rev Biochem. 1997;66:863–917. [PubMed]
  • Palmieri F. Mitochondrial carrier proteins. FEBS Lett. 1994 Jun 6;346(1):48–54. [PubMed]
  • Palmisano A, Zara V, Hönlinger A, Vozza A, Dekker PJ, Pfanner N, Palmieri F. Targeting and assembly of the oxoglutarate carrier: general principles for biogenesis of carrier proteins of the mitochondrial inner membrane. Biochem J. 1998 Jul 1;333(Pt 1):151–158. [PMC free article] [PubMed]
  • Pfanner N, Neupert W. Distinct steps in the import of ADP/ATP carrier into mitochondria. J Biol Chem. 1987 Jun 5;262(16):7528–7536. [PubMed]
  • Pfanner N, Hoeben P, Tropschug M, Neupert W. The carboxyl-terminal two-thirds of the ADP/ATP carrier polypeptide contains sufficient information to direct translocation into mitochondria. J Biol Chem. 1987 Nov 5;262(31):14851–14854. [PubMed]
  • Rassow J, Maarse AC, Krainer E, Kübrich M, Müller H, Meijer M, Craig EA, Pfanner N. Mitochondrial protein import: biochemical and genetic evidence for interaction of matrix hsp70 and the inner membrane protein MIM44. J Cell Biol. 1994 Dec;127(6 Pt 1):1547–1556. [PMC free article] [PubMed]
  • Ryan KR, Jensen RE. Protein translocation across mitochondrial membranes: what a long, strange trip it is. Cell. 1995 Nov 17;83(4):517–519. [PubMed]
  • Ryan KR, Menold MM, Garrett S, Jensen RE. SMS1, a high-copy suppressor of the yeast mas6 mutant, encodes an essential inner membrane protein required for mitochondrial protein import. Mol Biol Cell. 1994 May;5(5):529–538. [PMC free article] [PubMed]
  • Saraste M, Walker JE. Internal sequence repeats and the path of polypeptide in mitochondrial ADP/ATP translocase. FEBS Lett. 1982 Aug 2;144(2):250–254. [PubMed]
  • Schägger H, von Jagow G. Blue native electrophoresis for isolation of membrane protein complexes in enzymatically active form. Anal Biochem. 1991 Dec;199(2):223–231. [PubMed]
  • Schatz G. The protein import system of mitochondria. J Biol Chem. 1996 Dec 13;271(50):31763–31766. [PubMed]
  • Schneider HC, Berthold J, Bauer MF, Dietmeier K, Guiard B, Brunner M, Neupert W. Mitochondrial Hsp70/MIM44 complex facilitates protein import. Nature. 1994 Oct 27;371(6500):768–774. [PubMed]
  • Schneider HC, Westermann B, Neupert W, Brunner M. The nucleotide exchange factor MGE exerts a key function in the ATP-dependent cycle of mt-Hsp70-Tim44 interaction driving mitochondrial protein import. EMBO J. 1996 Nov 1;15(21):5796–5803. [PMC free article] [PubMed]
  • Sirrenberg C, Bauer MF, Guiard B, Neupert W, Brunner M. Import of carrier proteins into the mitochondrial inner membrane mediated by Tim22. Nature. 1996 Dec 12;384(6609):582–585. [PubMed]
  • Sirrenberg C, Endres M, Fölsch H, Stuart RA, Neupert W, Brunner M. Carrier protein import into mitochondria mediated by the intermembrane proteins Tim10/Mrs11 and Tim12/Mrs5. Nature. 1998 Feb 26;391(6670):912–915. [PubMed]
  • Smagula C, Douglas MG. Mitochondrial import of the ADP/ATP carrier protein in Saccharomyces cerevisiae. Sequences required for receptor binding and membrane translocation. J Biol Chem. 1988 May 15;263(14):6783–6790. [PubMed]
  • Wachter C, Schatz G, Glick BS. Role of ATP in the intramitochondrial sorting of cytochrome c1 and the adenine nucleotide translocator. EMBO J. 1992 Dec;11(13):4787–4794. [PMC free article] [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • Protein
    Published protein sequences
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...