Figure 5.

TOM–TIM interaction for protein import.A, presequence-containing proteins targeted to the mitochondrial matrix require coordinated transfer from the TOM to the TIM23 complex. First, Tom20 recognizes the positively charged presequence and transfers it to Tom22 (step 1). The latter directs the polypeptide to the negatively charged lumen of Tom40 for transport across the OMM through favorable electrostatic interactions (step 2). At the IMS face, the presequence is recognized and bound by the extramembranous domain of Tim50, for transfer to the TIM23 complex (steps 3–4). MPP cleaves the presequence, releasing the mature folded protein in the mitochondrial matrix. The presequence handover from TOM to TIM23 is coordinated by Tom22 and Tim50 in the OMM and IMM, respectively. The matrix face of TIM23 also contains Tim44 and the ATP-dependent presequence translocase-associated motor (PAM). Figure inspired from (68). B, import of multipass transmembrane helical carrier proteins of the IMM is executed by the TIM22 complex. Tom70 recognizes the signal sequence and Tom40 imports it across the OMM (steps 1–2). At the IMS face, small Tim9–Tim10 chaperones capture and retain the polypeptide in its unfolded state (14). The hybrid Tim9–Tim10–Tim12 complex that is formed next, hands over the polypeptide to the TIM22 complex, which successfully inserts and folds the carrier protein into the IMM (steps 3–4). Figure inspired from (63). Both the TOM–TIM import processes are driven by the potential across the IMM and are ATP-independent. IMM, inner mitochondrial membrane; IMS, intermembrane space; MPP, mitochondrial processing peptidase; OMM, outer mitochondrial membrane; TIM, translocase of the inner mitochondrial membrane; TOM, translocase of the outer mitochondrial membrane.