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. 1996 Feb 1;15(3):479–487.

Internal targeting signal of the BCS1 protein: a novel mechanism of import into mitochondria.

H Fölsch 1, B Guiard 1, W Neupert 1, R A Stuart 1
PMCID: PMC449966  PMID: 8599931

Abstract

The BCS1 protein is anchored in the mitochondrial inner membrane via a single transmembrane domain and has an N(out)-C(in) topology. Unlike the majority of nuclear encoded mitochondrial preproteins, the BCS1 protein does not contain an N-terminal targeting sequence. A positively charged segment of amino acids which is located immediately C-terminal to the transmembrane domain acts as an internal targeting signal. In order to function, we postulate that this sequence co-operates with the transmembrane domain to form a tight hairpin loop structure. This loop is translocated across the inner membrane via the MIM/mt-Hsp70 machinery in a membrane potential-dependent manner. This novel mechanism of import and sorting of the BCS1 protein is proposed to represent a more general mechanism used by a number of inner membrane proteins.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berthold J., Bauer M. F., Schneider H. C., Klaus C., Dietmeier K., Neupert W., Brunner M. The MIM complex mediates preprotein translocation across the mitochondrial inner membrane and couples it to the mt-Hsp70/ATP driving system. Cell. 1995 Jun 30;81(7):1085–1093. doi: 10.1016/s0092-8674(05)80013-3. [DOI] [PubMed] [Google Scholar]
  2. Blom J., Dekker P. J., Meijer M. Functional and physical interactions of components of the yeast mitochondrial inner-membrane import machinery (MIM). Eur J Biochem. 1995 Aug 15;232(1):309–314. doi: 10.1111/j.1432-1033.1995.tb20813.x. [DOI] [PubMed] [Google Scholar]
  3. Blom J., Kübrich M., Rassow J., Voos W., Dekker P. J., Maarse A. C., Meijer M., Pfanner N. The essential yeast protein MIM44 (encoded by MPI1) is involved in an early step of preprotein translocation across the mitochondrial inner membrane. Mol Cell Biol. 1993 Dec;13(12):7364–7371. doi: 10.1128/mcb.13.12.7364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boyd D., Beckwith J. The role of charged amino acids in the localization of secreted and membrane proteins. Cell. 1990 Sep 21;62(6):1031–1033. doi: 10.1016/0092-8674(90)90378-r. [DOI] [PubMed] [Google Scholar]
  5. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  6. Cao G., Dalbey R. E. Translocation of N-terminal tails across the plasma membrane. EMBO J. 1994 Oct 3;13(19):4662–4669. doi: 10.1002/j.1460-2075.1994.tb06789.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Emr S. D., Vassarotti A., Garrett J., Geller B. L., Takeda M., Douglas M. G. The amino terminus of the yeast F1-ATPase beta-subunit precursor functions as a mitochondrial import signal. J Cell Biol. 1986 Feb;102(2):523–533. doi: 10.1083/jcb.102.2.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fourie A. M., Sambrook J. F., Gething M. J. Common and divergent peptide binding specificities of hsp70 molecular chaperones. J Biol Chem. 1994 Dec 2;269(48):30470–30478. [PubMed] [Google Scholar]
  9. Glick B. S., Brandt A., Cunningham K., Müller S., Hallberg R. L., Schatz G. Cytochromes c1 and b2 are sorted to the intermembrane space of yeast mitochondria by a stop-transfer mechanism. Cell. 1992 May 29;69(5):809–822. doi: 10.1016/0092-8674(92)90292-k. [DOI] [PubMed] [Google Scholar]
  10. Herrmann J. M., Koll H., Cook R. A., Neupert W., Stuart R. A. Topogenesis of cytochrome oxidase subunit II. Mechanisms of protein export from the mitochondrial matrix. J Biol Chem. 1995 Nov 10;270(45):27079–27086. doi: 10.1074/jbc.270.45.27079. [DOI] [PubMed] [Google Scholar]
  11. Maarse A. C., Blom J., Grivell L. A., Meijer M. MPI1, an essential gene encoding a mitochondrial membrane protein, is possibly involved in protein import into yeast mitochondria. EMBO J. 1992 Oct;11(10):3619–3628. doi: 10.1002/j.1460-2075.1992.tb05446.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nobrega F. G., Nobrega M. P., Tzagoloff A. BCS1, a novel gene required for the expression of functional Rieske iron-sulfur protein in Saccharomyces cerevisiae. EMBO J. 1992 Nov;11(11):3821–3829. doi: 10.1002/j.1460-2075.1992.tb05474.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Pelham H. R., Jackson R. J. An efficient mRNA-dependent translation system from reticulocyte lysates. Eur J Biochem. 1976 Aug 1;67(1):247–256. doi: 10.1111/j.1432-1033.1976.tb10656.x. [DOI] [PubMed] [Google Scholar]
  14. Rojo E. E., Stuart R. A., Neupert W. Conservative sorting of F0-ATPase subunit 9: export from matrix requires delta pH across inner membrane and matrix ATP. EMBO J. 1995 Jul 17;14(14):3445–3451. doi: 10.1002/j.1460-2075.1995.tb07350.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Scherer P. E., Manning-Krieg U. C., Jenö P., Schatz G., Horst M. Identification of a 45-kDa protein at the protein import site of the yeast mitochondrial inner membrane. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11930–11934. doi: 10.1073/pnas.89.24.11930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Schleyer M., Schmidt B., Neupert W. Requirement of a membrane potential for the posttranslational transfer of proteins into mitochondria. Eur J Biochem. 1982 Jun 15;125(1):109–116. doi: 10.1111/j.1432-1033.1982.tb06657.x. [DOI] [PubMed] [Google Scholar]
  17. Schmidt B., Wachter E., Sebald W., Neupert W. Processing peptidase of Neurospora mitochondria. Two-step cleavage of imported ATPase subunit 9. Eur J Biochem. 1984 Nov 2;144(3):581–588. doi: 10.1111/j.1432-1033.1984.tb08505.x. [DOI] [PubMed] [Google Scholar]
  18. Schneider H. C., Berthold J., Bauer M. F., Dietmeier K., Guiard B., Brunner M., Neupert W. Mitochondrial Hsp70/MIM44 complex facilitates protein import. Nature. 1994 Oct 27;371(6500):768–774. doi: 10.1038/371768a0. [DOI] [PubMed] [Google Scholar]
  19. Ungermann C., Neupert W., Cyr D. M. The role of Hsp70 in conferring unidirectionality on protein translocation into mitochondria. Science. 1994 Nov 18;266(5188):1250–1253. doi: 10.1126/science.7973708. [DOI] [PubMed] [Google Scholar]
  20. von Heijne G. Control of topology and mode of assembly of a polytopic membrane protein by positively charged residues. Nature. 1989 Oct 5;341(6241):456–458. doi: 10.1038/341456a0. [DOI] [PubMed] [Google Scholar]
  21. von Heijne G. Mitochondrial targeting sequences may form amphiphilic helices. EMBO J. 1986 Jun;5(6):1335–1342. doi: 10.1002/j.1460-2075.1986.tb04364.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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