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