This article reviews a report about one of the TIM proteins, but also gives a nice overview of the issues regarding import.
Abstract: After reconstitution into liposomes, Tim23p, a mitochondrial inner membrane protein required for protein import, forms an aqueous pore that is activated by a transmembrane potential and mitochondrial targeting peptides. A report in this issue suggests that proteins are translocated into the mitochondrial matrix through a channel formed by Tim23p. These data also suggest a mechanism by which protein import can occur without disrupting the permeablility barrier of the inner membrane.
Protein transport machinery
The mitochondrion is a structurally complex organelle, with both an outer and an inner membrane, an intermembrane space (IMS) and a matrix. Protein import is a multi-step pathway that includes the binding of precursor proteins to surface receptors on the outer membrane, translocation of the precursor across one or both mitochondrial membranes, and folding and assembly of the imported protein inside the mitochondrion1, 2, 3, 4 (Fig. 1). Proteins destined for the matrix, IM, or IMS are all transported through the outer membrane via the TOM complex. Electron microscopy indicates that each TOM complex contains two or three holes with diameters 20 Å (ref. 6), suggesting that the complex forms one or more aqueous pores in the OM through which substrate proteins move6, 7. The Tom40 protein, a member of the TOM complex, appears to be the pore-forming subunit of the complex6, 7. In the inner membrane, the TIM23 complex consists of at least two integral membrane proteins, Tim23p and Tim17p8, 9, 10, 11. Tim23p and Tim17p are multi-spanning membrane proteins with significant homology to each other, and both are adjacent to a precursor in transit across the IM11, 12. The matrix-localized Tim44 protein binds to the TIM23 complex, and the mitochondrial Hsp70 (mtHsp70) associates with the TIM23 complex via Tim44p4. Tim44p and mtHsp70 are required for the ATP-dependent movement of the substrate into the matrix3, 13.