TOMTIMkomplexen

TOMTIMkomplexen refers to the coordinated translocase system that moves most proteins from the cytosol into mitochondria, comprising the TOM (translocase of the outer mitochondrial membrane) and TIM (translocase of the inner mitochondrial membrane) complexes. This system is essential for mitochondrial biogenesis and function, as the majority of mitochondrial proteins are synthesized in the cytosol and must be imported in an unfolded state.

The TOM complex sits in the outer membrane and serves as the initial gateway. It features receptor subunits such as Tom20 and Tom70 that recognize targeting signals, a central receptor like Tom22, and the β-barrel channel formed by Tom40 through which precursors pass into the intermembrane space. Additional small Tom subunits assist in assembly and regulation. The TOM complex often cooperates with intermembrane space factors to route proteins to their final destinations.

The TIM complexes operate in the inner mitochondrial membrane and come in several forms, with TIM23 and TIM22 being the best characterized. The TIM23 complex translocates proteins bearing N-terminal targeting presequences into the matrix or inserts them into the inner membrane, aided by a motor that includes mitochondrial Hsp70 and associated co-chaperones. The TIM22 complex handles the insertion of multi-pass inner membrane carrier proteins without N-terminal presequences. Small Tim chaperones in the intermembrane space guide hydrophobic precursors between TOM and TIM23 or TIM22. Tim50 serves as a receptor component for TIM23, helping to recognize incoming precursors.

Coordination between TOM and TIM, energy input from the membrane potential and ATP-dependent motors, and auxiliary pathways ensure accurate sorting and maturation of mitochondrial proteins. Defects in TOM or TIM components can impair protein import and are implicated in mitochondrial disorders and neurodegenerative diseases.