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#mitochondrial protein import

3 public questions tagged with this topic.

Protein Sorting and Trafficking

What is the function of Hsp70 chaperones during mitochondrial protein import?

Cytosolic steps preceding mitochondrial import require chaperoning maintain precursors loosely folded translocation competent capable threading narrow TOM 20 angstrom channel. Nascent chains emerging ribosome contain hydrophobic segments aggregation-prone aqueous cytosol. Cytosolic Hsp70 family mainly Ssa1-4 yeast and HSPA1A HSPA8 mammals with co-chaperones Ydj1 Sis1 J-domain stimulating ATPase nucleotide exchange Sse1 Bag family bind exposed hydrophobic patches substrate binding domain ATP-dependent holdase preventing misfolding self-association aggregation delivering precursors Tom70 recepto

Ref: Young et al., Cell 2003: Cytosolic Hsp70 chaperones mitochondrial precursor aggregation prevention.

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Protein Sorting and Trafficking

The TIM23 complex is primarily involved in:

Inner mitochondrial membrane protein import presequence pathway uses TIM23 complex distinct carrier TIM22. After crossing outer membrane Tom40 pore proteins bearing N-terminal positively charged amphipathic presequence arginine lysine hydroxylated recognized via Tim50 IMS receptor presequence groove interacting Tim23 channel. TIM23 complex comprises Tim23 voltage-gated aqueous channel C-terminal domain four transmembrane helices regulated Tim50, Tim17 paralog stabilizing pore, Tim21 bridging respiratory chain, Mgr2 gating Tim50. Driving forces two components: membrane potential Delta psi negat

Ref: Neupert & Herrmann, Annu Rev Biochem 2007: TIM23 imports proteins into mitochondrial matrix via motor.

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Protein Sorting and Trafficking

Which complex is responsible for mitochondrial protein import into the outer membrane?

Mitochondrial proteome exceeds 1000 proteins but mitochondrial genome encodes only 13 hydrophobic subunits humans requiring massive import nuclear encoded precursors cytosolic ribosomes. Entry gateway TOM complex translocase outer membrane central hub 400-500 kDa. Core beta-barrel channel Tom40 19 beta strands hydrophilic pore about 20 angstrom unfolded polypeptide passage. Associated receptors provide specificity: Tom20 tetratricopeptide clamps amphipathic presequence hydrophobic face, Tom70 clamp binds internal hydrophobic signals carriers via Hsp70/Hsp90 chaperone docking, Tom22 central org

Ref: Wiedemann & Pfanner, Annu Rev Biochem 2017: TOM complex outer membrane import machinery.

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