Recombinant Rat Mitochondrial import inner membrane translocase subunit Tim23 (Timm23)

Introduction to Recombinant Rat Mitochondrial Import Inner Membrane Translocase Subunit Tim23 (Timm23)

The Recombinant Rat Mitochondrial import inner membrane translocase subunit Tim23 (Timm23) is a vital component of the protein translocation machinery in mitochondria . Mitochondria, essential organelles in eukaryotic cells, rely on the import of almost all of their constituent proteins, which are synthesized in the cytosol, across their double-membrane envelope . The TIM23 complex, a conserved protein translocase, facilitates the import of presequence-containing proteins (preproteins) into the mitochondrial matrix and inner membrane .

Function and Structure of the TIM23 Complex

The TIM23 complex mediates the translocation of preproteins across and their insertion into the mitochondrial inner membrane . This complex is essential for mitochondrial biogenesis, as it imports the majority of proteins required for mitochondrial function from the cytosol .

Role of Individual Subunits

• Tim23: Integral to the TIM23 complex, it is essential for the translocation of preproteins into mitochondria . It was initially believed to form part of the protein-conducting channel, but structural analysis suggests it has a structural role in the complex .

• Tim17: Forms the protein translocation path within the TIM23 complex .

• Tim50: Promotes the closure of the Tim23 channel in the absence of precursor proteins, allowing tight regulation .

• Tim21: Modulates the activity of the TIM23 complex and is involved in the import of proteins into the matrix .

Interaction with Mutant Huntingtin (Htt)

Research indicates that mutant Huntingtin (Htt), associated with Huntington's disease (HD), interacts with the TIM23 complex, which inhibits protein import in isolated brain mitochondria . The N-terminal 17 amino acids (N17) of Htt are crucial for its subcellular localization and interaction with the TIM23 complex . Mutant Htt specifically associates with the Tim23 subunit . Inhibition of mitochondrial protein import by mutant Htt is an early pathogenic defect that leads to neuronal death .

TIMM50 and Its Impact on TIM23 Complex

TIMM50, another component, is also vital for the stability of the TIM23 core complex . Studies involving TIMM50 mutations in human fibroblasts have shown significant decreases in TIM23 core protein levels (TIMM50, TIMM17A/B, and TIMM23) . Deficiencies in TIMM50 can lead to declined respiration rates, reduced cellular ATP levels, and defective mitochondrial trafficking in neuronal processes, contributing to neurological defects .

Remodeling of the TIM23 Complex

The TIM23 complex undergoes active remodeling to sort preproteins into different mitochondrial subcompartments . Subunits like Tim21 and Pam17 modulate its activity, indicating that the TIM23 complex functions as a single structural and functional unit .