FIGURE 2.

Mitochondrial import and proteostatic control. (A) Trafficking routes of mitochondrial proteins. Mitochondrial proteins include soluble proteins of the IMS/ICS and matrix (green), α-helical membrane proteins of the MOM and MIM (yellow) and β-barrel proteins of the MOM (cyan). Trafficking routes are depicted for nuclear-encoded proteins (solid lines) and mitochondrial-encoded proteins (dashed line). The major protein transport complexes include the translocase of the outer membrane (TOM) complex, the mitochondrial import (MIM) complex, the sorting and assembly machinery (SAM) complex, translocases of the inner membrane 22 and 23 (TIM22 and TIM23, respectively), the mitochondrial IMS import and assembly (MIA) complex, and the oxidase assembly (OXA) insertase. The trafficking of MTS-containing precursors via the TIM23 pathway is denoted by the thick arrows. (B) Targeting and topogenic sequences of TIM23 substrates. The MTSs are depicted in gray as containing basic (+) and hydrophobic (ϕ) residues. The stop-transfer segment is depicted in black. (C) The mammalian TIM23 import, processing, and quality control machinery. Components of the biogenesis machinery are categorized as: (i) chaperones that regulate the targeting of precursors from the cytosol to the mitochondrion (violet), (ii) outer membrane (TOM and SAM) complexes (green), (iii) TIM23^MOTOR and TIM23^SORT complexes (yellow), (iv) proteases that process TIM23 substrates (cyan), (v) matrix chaperones that mediate the folding of TIM23 substrates (orange), and (vi) proteases that mediate the degradation of mitochondrial proteins (red). See Supplementary Table S1 for a listing of all relevant proteins.