Fig. 3.

Pathways to the mitochondrial matrix and inner membrane. All proteins destined for the matrix or inner membrane cross the outer membrane through the TOM translocon (blue). Two receptor proteins, Tom20 (20) and Tom70 (70), which are part of the TOM complex, engage these proteins on the cytosolic side of the outer membrane. These proteins then use one of the two translocases present in the mitochondrial inner membrane: TIM22 (green) and TIM23 (brown). Proteins that are particularly hydrophobic, such as metabolite carrier integral membrane proteins, typically use the Tom70 receptor, then the TIM22 translocon, from which they are laterally transferred into the inner membrane (black arrow). Proteins with N-terminal cleavable targeting sequences typically use the presequence pathway: the Tom20 receptor, then the TIM23 translocon (red arrow). The membrane potential across the inner membrane (∆ψ) drives the positively charged presequence across the membrane. Three routes of proteins utilizing the TIM23 translocon: (i) the presequence associated motor (PAM) drives the remainder of the protein in the matrix; (ii) proteins with “stop transfer” sequences move laterally into the inner membrane; (iii) proteins with multiple domains may be partially imported by PAM and then move laterally into the membrane via the signal of an internal stop-transfer sequence