Tom40, the pore-forming component of the protein-conducting TOM channel inthe outer membrane of mitochondria

Tom40 is the main component of the preprotein translocase of the outer memb rane of mitochondria (TOM complex). We have isolated Tom40 of Neurospora cr assa by removing the receptor Tom22 and the small Tom components Tom6 and T om7 from the purified TOM core complex. Tom40 is organized in a high molecu lar mass complex of similar to 350 kD. It forms a high conductance channel. Mitochondrial presequence peptides interact specifically with Tom40 recons tituted into planar lipid membranes and decrease the ion flow through the p ores in a voltage-dependent manner. The secondary structure of Tom40 compri ses similar to 31% beta -sheet, 22% alpha -helix, and 47% remaining structu re as determined by circular dichroism measurements and Fourier transform i nfrared spectroscopy. Electron microscopy of purified Tom40 revealed partic les primarily with one center of stain accumulation. They presumably repres ent an open pore with a diameter of similar to2.5 nm, similar to the pores found in the TOM complex. Thus, Tom40 is the core element of the TOM transl ocase; it forms the protein-conducting channel in an oligomeric assembly.