Skip to main content
SpringerLink
Log in

The biogenesis and function of eukaryotic porins

  • Multi-author Review
  • Published:
Experientia Aims and scope Submit manuscript

Summary

Like most other mitochondrial proteins porin is synthesized in the cytosol and imported posttranslationally into the outer mitochondrial membrane. This transport follows the general rules for mitochondrial, protein import with a few aberrations: a) porin contains an,uncleaved NH2-terminal signal sequence, b) also its carboxyterminus might be involved in the import process, and c) this transport does not seem to require a membrane potential Δψ, although it is ATP-dependent. Most likely the actual import step occurs at contact sites between the outer and the inner mitochondrial membrane and involved at least one receptor protein.

Although porin is known to be the major gate through the outer mitochondrial membrane, its absence only causes transient respiratory problems in yeast cells. This could mean a) that there is a bypass for some mitochondrial functions in the cytosol and/or b) that there are alternative channel proteins in the outer membrane. The first idea is supported by the overexpression of cytosolic virus-like particles in yeast cells lacking porin and the second by the occurrence of residual pore activity in mitochondrial outer membrane purified from porinless mutant cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Benz, R., Porin from bacterial and mitochondrial outer membranes. CRC Cr. Rev. Biochem.19 (1985) 145–190.

    Article  CAS  Google Scholar 

  2. Benz, R., Ludwig, O., de Pinto, V., and Palmieri, F., Permeability properties of mitochondrial porins of different eukaryotic cells, in: Achievements and Perspectives of Mitochondrial Research, vol. 1: Bioenergetics, pp. 317–327. Eds E. Quagliariello et al. Elsevier Science Publishers B.V. (Biomedical Division), Amsterdam 1985.

    Google Scholar 

  3. Chen, W.J., and Douglas, M., The role of protein structure in the mitochondrial import pathway: unfolding of mitochondrially bound precursors is required for membrane translocation. J. biol. Chem.262 (1987) 15605–15609.

    Article  CAS  PubMed  Google Scholar 

  4. Chirico, W. J., Waters, M. G., and Blobel, G., 70 k heat shock related proteins stimulate protein translocation into microsomes. Nature332 (1988) 805–810.

    Article  CAS  PubMed  Google Scholar 

  5. Colombini, M., A candidate for the permeability pathway of the outer mitochondrial membrane. Nature279 (1979) 643–645.

    Article  CAS  PubMed  Google Scholar 

  6. Colombini, M., Pore size and properties of channels from mitochondria isolated fromNeurospora crassa. J. Membr. Biol.53 (1980) 79–84.

    Article  CAS  Google Scholar 

  7. Deisenhofer, J., Epp, O., Miki, K., Huber R., and Michel, H., Structure of the protein subunits in the photosynthetic reaction centre ofRhodopseudomonas viridis at 3A resolution. Nature318 (1985) 618–624.

    Article  CAS  PubMed  Google Scholar 

  8. Deshaies, R. J., Koch, B. D., and Schekman, R., The role of stress proteins in membrane biogenesis. TIBS13 (1988) 384–388.

    CAS  PubMed  Google Scholar 

  9. Deshaies, R. J., Koch, B. D., Werner-Washburne, M., Craig, E. A., and Schekman, R., A subfamily of stress proteins facilitates translocation of secretory and mitochondrial precursor polypeptides. Nature332 (1988) 800–805.

    Article  CAS  PubMed  Google Scholar 

  10. Dihanich, M., Schmid, A., Oppliger W., and Benz, R., Identification of a new pore in the mitochondrial outer membrane of a porin deficient yeast mutant. Eur. J. Biochem.181 (1989) 703–708.

    Article  CAS  PubMed  Google Scholar 

  11. Dihanich, M., Suda, K., and Schatz, G., A yeast mutant lacking mitochondrial porin is respiratory-deficient but can recover respiration with simultaneous accumulation of an 86-kd extramitochondrial protein. EMBO J.6 (1987) 723–728.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Dihanich, M., Van Tuinen, E., Lambris, J. D., and Marshallsay, B., Accumulation of viruslike particles in a yeast mutant lacking a mitochondrial pore protein. Molec. Cell. Biol.9 (1989) 1100–1108.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Eilers, M., Hwang, S., and Schatz, G., Unfolding and refolding of a purified precursor protein during import into isolated mitochondria. EMBO J.7 (1988) 1139–1145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Eilers, M., Oppliger, W., and Schatz, G., Both ATP and an energized inner membrane are required to import a purified precursor protein into mitochondria. EMBO J.6 (1987) 1073–1077.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Eilers, M., and Schatz, G., Binding of a specific ligand inhibits import of a purified precursor protein into mitochondria Nature322 (1986) 228–232.

    Article  CAS  PubMed  Google Scholar 

  16. Eilers, M., and Schatz, G., Protein unfolding and the energetics of protein translocation across biological membranes. Cell52 (1988) 481–483.

    Article  CAS  PubMed  Google Scholar 

  17. Freitag, H., Janes, M., and Neupert, W., Biosynthesis of mitochondrial porin and insertion into the mitochondrial membrane ofNeurospora crassa. Eur. J. Biochem.126 (1982) 197–202.

    Article  CAS  PubMed  Google Scholar 

  18. Freitag, H., Neupert, W., and Benz, R., Purification and characterization of a pore protein of the outer mitochondrial membrane fromNeurospora crassa. Eur. J. Biochem.123 (1982) 629–636.

    Article  CAS  PubMed  Google Scholar 

  19. Garoff, H., Using recombinant DNA techniques to study protein targeting in the eukaryotic cell. A. Rev. Cell Biol.1 (1985) 403–445.

    Article  CAS  Google Scholar 

  20. Gasser, S., Daum, G., and Schatz, G., Import of proteins into mitochondria: energy-dependent uptake of precursors by isolated mitochondria. J. biol. Chem.257 (1982), 13034–13041.

    Article  CAS  PubMed  Google Scholar 

  21. Gasser, S., and Schatz, G., Import of proteins into mitochondria:in vitro studies on the biogenesis of the outer membrane. J. biol. Chem.258 (1983) 3427–3430.

    Article  CAS  PubMed  Google Scholar 

  22. Hamajima, S., Sakaguchi, M., Mihara, K., Ono, S., and Sato, R., Both amino-and carboxy-terminal portions are required for insertion of porin into the outer mitochondrial membrane. J. Biochem.104 (1988) 362–367.

    Article  CAS  PubMed  Google Scholar 

  23. Hase, T., Müller, U., Riezman, H., and Schatz, G., A 70-kd protein of the yeast mitochondrial outer membrane is targeted and anchored via its extreme amino terminus. EMBO J.3 (1984) 3157–3164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hase, T., Riezman, H., Suda, K., and Schatz, G., Import of proteins into mitochondria: nucleotide sequence of the gene for a 70-kd protein of the yeast mitochondrial outer membrane. EMBO J.2 (1983) 2169–2172.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hay, R., Boehni, P., and Gasser, S., How mitochondria import proteins. Biochim. biophys. Acta779 (1984) 65–87.

    Article  CAS  PubMed  Google Scholar 

  26. Hurt, E. C., Unravelling the role of ATP in posttranslational protein translocation. TIBS12 (1987) 369–370.

    Google Scholar 

  27. Hurt, E. C., Müller, U., and Schatz, G., The first twelve amino acids of a yeast mitochondrial outer, membrane protein can direct a nuclear-encoded cytochrome oxidase subunit to the mitochondrial inner membrane. EMBO J.4 (1985a) 3509–3518.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hurt, E.C., Pesold-Hurt, B., Suda, S., Oppliger, W., and Schatz, G., The first twelve amino acids (less than half of the pre-sequence) of an imported mitochondrial protein can direct mouse cytosolic dihydrofolate reductase into the yeast mitochondrial matrix. EMBO J.4 (1985b) 2061–2068.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Keng, T., Alani, E., and Guarente, L., The nine amino-terminal residues of δ-aminolevulinate synthase direct β-galactosidase into the mitochondrial matrix. Molec. cell. Biol.6 (1986) 355–364.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Kleene, R., Pfanner, N., Pfaller, R., Link, T.A., Sebald, W., Neupert, W., and Tropschug, M., Mitochondrial porin ofNeurospora crassa: cDNA cloning, in vitro expression and import into mitochondria. EMBO J.6 (1987) 2627–2633.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Linden, M., Gellerfors, P., and Nelson, B.D., Purification of a protein having pore forming activity from the rat liver mitochondrial outer membrane. Biochem. J.208 (1982) 77–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Maccechini M.-L., Rudin, Y., Blobel, G., and Schatz, G., Import of proteins into mitochondria: precursor forms of the extramitochondrially made F1-ATPase subunits in yeast. Proc. natl Acad. Sci. USA76 (1979) 343–347.

    Article  Google Scholar 

  33. Malamed, S., and Recknagel, R.O., The osmotic behavior of the sucrose-inaccessible space of mitochondrial pellets from rat liver. J. biol. Chem.234 (1959) 3027–3030.

    Article  CAS  PubMed  Google Scholar 

  34. Michejda, J., Guo, X.J., and Lauquin, G.J.M., Bioenergetic consequences of the lack of mitochondrial porin: identification of a putative new pore, in: Anion Carriers of Mitochondrial Membranes, pp. 225–235. Eds A. Azzi et al. Springer, Heidelberg/New York 1989.

    Chapter  Google Scholar 

  35. Mihara, K., Blobel, G., and Sato, R., In vitro synthesis and integration into mitochondria of porin, a major protein of the outer mitochondrial membrane ofSaccharomyces cerevisiae. Proc. natl Acad. Sci. USA79 (1982) 7102–7106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Mihara, K., and Sato, R., Molecular cloning and sequencing of cDNA for yeast porin, an outer mitochondrial membrane protein: a search for targeting signal in the primary structure. EMBO J.4 (1985) 769–774.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Müller, G., and Zimmermann, R., Import of honeybee prepromelittin into the endoplasmic reticulum: energy requirements for membrane insertion. EMBO J.7 (1988) 639–648.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Nguyen, M., Bell, A.W., and Shore, G.W., Protein sorting between mitochondrial membranes specified by position of the stop-transfer domain. J. Cell Biol.106 (1988) 1499–1505.

    Article  CAS  PubMed  Google Scholar 

  39. O'Brien, R.L., and Brierly, G., Compartmentation of Heart Mitochondria. I. Permeability characteristics of isolated beef heart mitochondria. J. biol. Chem.240 (1965) 4527–4531.

    Article  CAS  PubMed  Google Scholar 

  40. Ohba, M., and Schatz, G., Protein import into yeast mitochondria is inhibited by antibodies raised against 45-kd proteins of the outer membrane. EMBO J.6 (1987a) 2109–2115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ohba, M., and Schatz, G., Disruption of the outer membrane restores protein import to trypsin-treated yeast mitochondria. EMBO J.6 (1987b) 2117–2122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ono, H., and Tuboi, S., Integration of porin synthesized in vitro into outer mitochondrial membranes. Eur. J. Biochem.168 (1987) 509–514.

    Article  CAS  PubMed  Google Scholar 

  43. Park, S., Liu, G., Topping, T.B., Cover, W.H., and Randall, L.L., Modulation of the folding pathways of exported proteins by the leader sequence. Science239 (1988) 1033–1035.

    Article  CAS  PubMed  Google Scholar 

  44. Pfaller, R., Freitag, H., Harmey, M.A., Benz, R., and Neupert, W., A water-soluble from of porin from the mitochondrial outer membrane ofNeurospora crassa. J. biol. Chem.260 (1985) 8188–8193.

    Article  CAS  PubMed  Google Scholar 

  45. Pfaller, R., and Neupert, W., High-affinity binding sites involved in the import of porin into mitochondria. EMBO J.6 (1987) 2635–2642.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Pfaller, R., Steger, H.F., Rassow, J., Pfanner, N., and Neupert, W., Import pathways of precursor proteins into mitochondria: multiple receptor sites are followed by a common membrane insertion site. J. Cell Biol.107 (1983) 2483–2490.

    Article  Google Scholar 

  47. Pfanner, N., Hartl, F.-U., Guiard, B., and Neupert, W., Mitochondrial precursor proteins are imported through a hydrophilic membrane environment. Eur. J. Biochem.169 (1987) 289–293.

    Article  CAS  PubMed  Google Scholar 

  48. Pfanner, N., and Neupert, W., Transport of proteins into mitochondria: a potassium diffusion potential is able to drive the import of ADP/ATP carrier. EMBO J.4 (1985) 2819–2825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Pfanner, N., Pfaller, R., Kleene, R., Ito, M., Tropschug, M., and Neupert, W., Role of ATP in mitochondrial protein import: conformational alteration of a precursor protein can substitute for ATP requirement. J. biol. Chem.263 (1988) 4049–4051.

    Article  CAS  PubMed  Google Scholar 

  50. Pfanner, N., Tropschug, M., and Neupert, W., Mitochondrial protein import: nucleoside triphosphates are involved in conferring importcompetence to precursors. Cell49 (1987) 815–823.

    Article  CAS  PubMed  Google Scholar 

  51. Pietras, D.F., Diamond, M.E., and Bruenn, J.A., Identification of a putative RNA dependent RNA polymerase encoded by a yeast double stranded RNA virus. Nucl. Acid Res.16 (1988) 6225.

    Article  CAS  Google Scholar 

  52. Randall, L.L., and Hardy, S.J.S., Correlation of competence for export within lack of tertiary structure of the mature species: a studyin vivo of maltose-binding protein inE. coli. Cell46 (1986) 921–928.

    Article  CAS  PubMed  Google Scholar 

  53. Riezman, H., Hase, T., van Loon, A.P.G.M., Grivell, L.A., Suda, K., and Schatz, G., Import of proteins into mitochondria: a 70 kilodalton outer membrane protein with a large carboxy-terminal deletion is still transported to the outer membrane. EMBO J.2 (1983c) 2161–2168.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Riezmann, H., Hay, R., Gasser S., Daum, G., Schneider G., Witte, C., and Schatz, G., The outer membrane of yeast mitochondria: isolation of outside-out sealed vesicles. EMBO J.2 (1983a) 1105–1111.

    Article  Google Scholar 

  55. Riezman, H., Hay, R., Witte, C., Nelson, N., and Schatz, G., Yest mitochondrial outer membrane specifically binds cytoplasmically synthesized precursors of mitochondrial proteins. EMBO J.2 (1983b) 1113–1118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Roise, D., Theiler, F., Horvath, S.J., Tomich, J.M., Richards, J.H., Allison, D.S., and Schatz, G., Amphiphilicity is essential for mitochondrial presequence function. EMBO J.7 (1988) 649–653.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Roos, N., Benz, R., and Brdiczka, D., Identification and characterization of the pore-forming protein in the outer membrane of rat liver mitochondria. Biochim. biophys. Acta686 (1982) 204–214.

    Article  CAS  PubMed  Google Scholar 

  58. Schatz, G., How mitochondria import proteins from the cytoplasm. FEBS Lett.103 (1979) 203–211.

    Article  CAS  PubMed  Google Scholar 

  59. Schatz, G., 17th Sir Hans Krebs Lecture: Signals guiding proteins to their correct locations in mitochondria. Eur. J. Biochem.165 (1987) 1–6.

    Article  CAS  PubMed  Google Scholar 

  60. Schein, S.J., Colombini, M., and Finkelstein, A., Reconstitution in planar lipid bilayers of a voltage-dependent anion-selective channel obtained from Paramecium mitochondria. J. Membr. Biol.30 (1976) 99–120.

    Article  CAS  PubMed  Google Scholar 

  61. Schleyer, M., and Neupert, W., Transport of proteins into mitochondria: translocational intermediates spanning contact sites between outer and inner membranes. Cell43 (1985) 339–350.

    Article  CAS  PubMed  Google Scholar 

  62. Schleyer, M., Schmidt, B., and Neupert, W., Requirements of a membrane potential for the posttranslational transfer of proteins in mitochondria. Eur. J. Biochem.125 (1982) 109–116.

    Article  CAS  PubMed  Google Scholar 

  63. Suissa, M., Suda, K., and Schatz, G., Isolation of the nuclear yeast genes for citrate synthase and fifteen other mitochondrial proteins by a new screening method. EMBO J.3 (1984) 1773–1781.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Teintze, M., and Neupert, W., Biosynthesis and assembly of mitochondrial proteins, in: Cell Membranes: Methods and Reviews, vol. 1, pp. 89–114. Eds E. Elson, W. Frazier and L. Glaser. Plenum Press, New York 1984.

    Google Scholar 

  65. Tipper, D.J., and Bostian, K.A., Double-stranded ribonucleic acid killer systems in yeasts. Microbiol. Rev.48 (1984) 125–156.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Tzagoloff, A., Mitochondria. Ed. P. Siekevitz, Plenum Press, New York 1982.

    Google Scholar 

  67. van Loon, A.P.G.M., Brändli, A.W., Pesold-Hurt, B., Blank, D., and Schatz, G., Transport of proteins to the mitochondrial intermembrane space: the ‘matrix-targeting’ and the ‘sorting’ domains in the cytochrome c1 presequence. EMBO J.6 (1987) 2433–2439.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Verner, K., and Lemire, B., Tight folding of a passenger protein can interfere with the targeting function of a mitochondrial presequence. EMBO J.8 (1989) 1491–1495.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Verner, K., and Schatz, G., Import of an incompletely folded precursor protein into isolated mitochondria requires an energized inner membrane, but no added ATP. EMBO J.6 (1987) 2449–2456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Verner, K., and Schatz, G., Protein translocation across membranes. Science241 (1988) 1307–1313.

    Article  CAS  PubMed  Google Scholar 

  71. Vestweber, D., and Schatz, G., A chimeric mitochondrial precursor protein with internal disulfide bridges blocks import of authentic precursors into mitochondria and allows quantitation of import sites. J. Cell Biol.107 (1988a) 2037–2043.

    Article  CAS  PubMed  Google Scholar 

  72. Vestweber, D., and Schatz, G., Mitochondria can import artificial precursor proteins containing a branched polypeptide chain or a carboxy-terminal stibene disulfonate. J. Cell Biol.107 (1988b) 2045–2049.

    Article  CAS  PubMed  Google Scholar 

  73. Wessels, H.P., and Spiess, M., Insertion of a multi-spanning membrane protein occurs sequentially and requires only one signal sequence. Cell55 (1988) 61–70.

    Article  CAS  PubMed  Google Scholar 

  74. Wickner, R.B., Double-stranded RNA replication in yeast: the killer system. A. Rev. Biochem.55 (1986) 373–395.

    Article  CAS  Google Scholar 

  75. Zalman, L.S., Nikaido, H., and Kagawa, Y., Mitochondrial outer membrane contains a protein producing nonspecific diffusion channels. J. biol. Chem.255 (1980) 1771–1774.

    Article  CAS  PubMed  Google Scholar 

  76. Zimmermann, R., Hennig, B., and Neupert, W., Different transport pathways of individual precursor proteins in mitochondria. Eur. J. Biochem.116 (1981) 445–460.

    Article  Google Scholar 

  77. Zwizinski, C., Schleyer, M., and Neupert, W., Transfer of proteins into mitochondria: precursor to the ADP/ATP carrier binds to receptor sites on isolated mitochondria. J. biol. Chem.258 (1983) 4071–4074.

    Article  CAS  PubMed  Google Scholar 

  78. Zwizinski, C., Schleyer, M., and Neupert, W., Proteinaceous receptors for the import of mitochondrial precursor proteins. J. biol. Chem.259 (1984) 7850–7856.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Friedrich-Miescher-Institute, P.O. Box 2543, CH-Basel, Switzerland

    M. Dihanich

Authors
  1. M. Dihanich
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dihanich, M. The biogenesis and function of eukaryotic porins. Experientia 46, 146–153 (1990). https://doi.org/10.1007/BF02027310

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02027310

Key words

Search

Navigation