Protein translocation to the mitochondria
About 30% of all cellular proteins are found in membranes, transported there as precursors by vesicular transport or tightly regulated translocase systems. In eukaryotic cells, mitochondrial membrane proteins undergo a sequence of chaperoned transfers across a dual membrane system prior to final assembly, utilising dedicated mitochondrial translocases. Transport of membrane-targeted precursors presents specific issues, most notably non-specific aggregation of transmembrane segments. At the same time, internal targeting signals must remain accessible to engage translocase receptors during serial changeovers.
The targeting and transfer of membrane-spanning transporters through the periplasm-like environment of the intermembrane space requires specialised translocase components. Our structures of Tim9-Tim10 revealed a modular propeller-like fold, suggesting a previously unanticipated mode of chaperone activity and serving as a model for deriving function. Achieving our objective of experimentally defining the interactions of mitochondrial carrier family precursors with translocase components would represent a significant step toward elucidating the pathway, and provides a direct means of establishing novel chaperone function.