Mechanisms of protein import into mitochondria

Pfanner, N., Hönlinger, A., Rassow, J., Ryan, M.T. and Voos, W.

Institut für Biochemie und Molekularbiologie, Universität Freiburg, Hermann-Herder-Strasse 7, D-79104 Freiburg, Germany

More than 95% of mitochondrial proteins are encoded by nuclear genes and synthesized on cytosolic polysomes (1). Targeting signals, often located in amino-terminal presequences, direct the preproteins to receptors on the mitochondrial surface. The preprotein translocase of the outer mitochondrial membrane, termed Tom, consists of at least eight different subunits that are organized in subcomplexes (2). Receptor subcomplexes (Tom20 and Tom70-Tom37) initially bind preproteins and transfer them to the General Import Pore (GIP) complex. The GIP complex of about 400 kDa contains the two essential proteins Tom40 (pore) and Tom22, and three small Tom proteins. After translocation through the pore and interaction with a trans binding site on the intermembrane space side, the preproteins are inserted into the inner membrane. This requires a membrane potential and the preprotein translocase of the inner membrane (Tim). The Tim core complex (channel) of about 90 kDa consists of the essential proteins Tim17 and Tim23 (3). Tim44 transiently associates with the core complex and acts as membrane anchor for the heat shock protein 70 of the matrix. Hsp70 directly binds preproteins and drives their import in an ATP-dependent reaction. Hsp70 seems to function by a mechanism that combines pulling and trapping of the preprotein (4). Moreover, Hsp70 may exert a regulatory function on the Tim core complex (3).

(1) Pfanner, N., Craig, E.A., and Hönlinger, A. (1997) Annu. Rev. Cell Dev. Biol. 13, in press.
(2) Dietmeier, K., Hönlinger, A., Bömer, U., Dekker, P.J.T., Eckerskorn, C., Lottspeich, F., Kübrich, M., and Pfanner, N. (1997) Nature 388, 195-200.
(3) Dekker, P.J.T., Martin, F., Maarse, A.C., Bömer, U., Müller, H., Guiard, B., Meijer, M., Rassow, J., and Pfanner, N. (1997) EMBO J. 16, 5408-5419.
(4) Voos, W., von Ahsen, O., Müller, H., Guiard, B., Rassow, J., and Pfanner, N. (1996) EMBO J. 15, 2668-2677.

LOCATION DATE TIME
Lecture Hall I Monday, April 6 05:50 pm