Abstract
The TIM23 complex mediates import of preproteins into mitochondria, but little is known of the mechanistic properties of this translocase. Here patch clamping reconstituted inner membranes allowed for first time insights into the structure and function of the preprotein translocase. Our findings indicate that the TIM23 channel has "twin pores" (two equal sized pores that cooperatively gate) thereby strikingly resembling TOM, the translocase of the outer membrane. Tim17p and Tim23p are homologues, but their functions differ. Tim23p acts as receptor for preproteins and may largely constitute the preprotein-conducting passageway. Conversely depletion of Tim17p induces a collapse of the twin pores into a single pore, whereas N terminus deletion or C terminus truncation results in variable sized pores that cooperatively gate. Further analysis of Tim17p mutants indicates that the N terminus is vital for both voltage sensing and protein sorting. These results suggest that although Tim23p is the main structural unit of the pore Tim17p is required for twin pore structure and provides the voltage gate for the TIM23 channel.
Highlights
Tipass membrane proteins carrying internal targeting signals, e.g. phosphate carrier, are inserted into the inner membrane by the TIM22 complex
We provide evidence that the TIM23 channel has a twin pore structure, like the the outer membrane (TOM) and TIM22 channels, and that Tim17p is vital to maintaining this structure
The TIM23 complex is responsible for translocation across or insertion into the inner membrane for many mitochondrial preproteins
Summary
Tipass membrane proteins carrying internal targeting signals, e.g. phosphate carrier, are inserted into the inner membrane by the TIM22 complex Those preproteins with cleavable N-terminal presequences that are destined for the matrix or the inner membrane are transported by the TIM23 translocase. Preproteins are recognized in the intermembrane space by the large C-terminal domain of Tim50p. This domain interacts with Tim23p and guides the precursor protein to the pore of the complex (8 –10). Tim17p was shown to be essential for both sorting of proteins into the inner membrane and translocation of precursor proteins into the matrix where Tim17p may provide a link between the TIM23 and PAM complexes [2]. Twin Pore Structure and Voltage Gating of the TIM23 Channel that the N terminus of Tim17p acts as the voltage sensor for the TIM23 complex
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