Mitochondrial ADP/ATP Carrier Associates with the Inner Membrane Presequence Translocase in a Stoichiometric Manner [Cell Biology]

August 14th, 2014 by Mehnert, C. S., Rampelt, H., Gebert, M., Oeljeklaus, S., Schrempp, S. G., Kochbeck, L., Guiard, B., Warscheid, B., van der Laan, M.

The majority of mitochondrial proteins are synthesized with amino-terminal signal sequences. The presequence translocase of the inner membrane (TIM23 complex) mediates the import of these preproteins. The essential TIM23 core complex closely cooperates with partner protein complexes like the import motor PAM and the respiratory chain. The inner mitochondrial membrane also contains a large number of metabolite carriers, yet their association with preprotein translocases has been controversial. We have performed a comprehensive SILAC-based analysis of the TIM23 interactome. Subsequent biochemical studies on identified partner proteins showed that the mitochondrial ADP/ATP carrier (AAC) associates with the membrane-embedded core of the TIM23 complex in a stoichiometric manner, revealing an unexpected connection of mitochondrial protein biogenesis to metabolite transport. Our data indicate that direct TIM23-AAC coupling may support preprotein import into mitochondria when respiratory activity is low.