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. 2021 Aug 2;22(15):8306. doi: 10.3390/ijms22158306

Figure 1.

Figure 1

Proteins are imported into mitochondria through multiple pathways. In yeast, protein precursors are synthesized by ribosomes in the cytosol and guided to the TOM complex on the OMM by chaperone Hsp70 and Hsp90, with the help of co-chaperones Ydj1 and Sti1. In the presequence pathway (left), precursors are first recognized by Tom20 of the TOM complex in the cytosol. Then, precursors are handed to Tom22 and subsequently brought through the Tom40 channel into the IMS. They are received by Tim50 of the TIM23 complex on the IMM and passed through to the matrix, with the help of the Tim44 protein and mtHsp70. The PAM complex prevents precursors from moving backwards out of the TIM23 complex. MPP cleaves the MTS to release proteins. Icp55 and Oct1 help remove any unstable amino acids from the N-terminal cleavage site of the proteins. Then, the presequence is degraded by PREP, and Oxa1 helps integrate mature proteins into the IMM when needed. In the pathways for non-cleavable proteins (right), carrier proteins (blue), proteins with cysteine residues (red), α-helical (purple), and β-barrel (brown) are shown. Carrier proteins pass through the TOM complex via the Tom40 channel into the IMS. Then, they are carried to their final location in the IMM by the TIM22 complex and other IMS chaperones. Precursors with cysteine residues also pass through the TOM complex via the Tom40 channel. Then, they are received by Mia40, which is regulated by Erv1, and helps create the disulfide bonds between cysteine residues and form mature proteins. α-helical precursors rely on Tom70 for recognition and do not localize to the IMS, as they are integrated into the OMM by the MIM complex. β-barrel precursors pass through the Tom40 pore into the IMS, and then moved to the SAM complex on the OMM via Tim chaperones, including Tim9, Tim10, and Tim12. Then, the SAM complex incorporates the mature proteins into the OMM. TOM: translocase of the outer membrane; OMM: Outer mitochondrial membrane; Hsp70: Heat-shock protein 70; Hsp90: Heat-shock protein 90; Ydj1: Yeast dnaJ 1; Sti1: Stress inducible protein 1; IMS: Intermembrane space; TIM: translocase of the inner membrane; IMM: Inner mitochondrial membrane; PAM: Presequence translocase-associated motor; MPP: Mitochondrial processing peptidase; MTS: Mitochondrial targeting sequence; Icp55: Intermediate cleaving peptidase 55; Oct1: Octapeptidyl aminopeptidase; PREP: Presequence peptidase; Oxa1: Mitochondrial inner membrane protein OXA1; Mia40: Mitochondrial intermembrane space import and assembly protein 40; Erv1: FAD-linked sulfhydryl oxidase ERV1; MIM: mitochondrial import complex; SAM: Sorting and assembly machinery.