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Protein Import into Mitochondria

Protein Import into Mitochondria

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MITOCHONDRIA
  • Generate energy for the cell
  • Have numerous metabolic functions
  • Comprise mitochondrial proteins (most encoded by nuclear genes)
  • Compartmental organization:
i. Outer membrane ii. Intermembrane space iii. Inner membrane iv. Matrix
IMPORT INTO MITOCHONDRIA • Prospective matrix protein unfolded in cytosol • Presequence: signal sequence at N-terminus; positively charged residues • TOM (translocase of outer membrane): import receptor and translocator • TIM (translocase of inner membrane): import receptor and translocator • Protein passes through TOM and enters intermembrane space; then passes through TIM to enter matrix
TOM-TIM alignment: research suggests that TIM tethers to the outer membrane and diffuses laterally until it comes into contact with the TOM/presequence complex
• Protein can enter matrix in energy-dependent manner (presequence cleaved by peptidase and chaperones assist in folding) • Protein's transmembrane domain can diffuse laterally out of TIM and embed in inner membrane
CLINICAL CORRELATION Neurodegenerative disorders • Often caused by defects in translocases • Genetic disorder in TIM production results in deafness and dystonia

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