Different import pathways through the mitochondrial intermembrane space for inner membrane proteins

Earlier work on the protein import system of yeast mitochondria has identif ied two soluble 70 kDa protein complexes in the intermembrane space. One co mplex contains the essential proteins Tim9p and Tim10p and mediates transpo rt of cytosolically-made metabolite carrier proteins from the outer to the inner membrane. The other complex contains the non-essential proteins Tim8p and Tim13p as well as loosely associated Tim9p; its function was unclear, but it interacted structurally or functionally with the Tim9p-Tim10p comple x. We now show that the two 70 kDa complexes each mediate the import of a d ifferent subset of integral inner membrane proteins and that they can trans fer these proteins to one of three different membrane insertion sites: the TIM22 complex, the TIM23 comples or an as yet uncharacterized insertion sit e. Yeast mitochondria thus use multiple pathways for escorting hydrophobic inner membrane proteins across the aqueous intermembrane space.