Mgr2 functions as lateral gatekeeper for preprotein sorting in the mitochondrial inner membrane
13.11.2014
Ieva R, Schrempp SG, Opali?ski L, Wollweber F, Höß P, Heißwolf AK, Gebert M, Zhang Y, Guiard B, Rospert S, Becker T, Chacinska A, Pfanner N, van der Laan M.
Mol Cell. 2014 Dec 4;56(5):641-52.
The TIM23 complex is the major preprotein translocase of the inner mitochondrial membrane. This intricate molecular machine imports nuclear-encoded mitochondrial preproteins that carry amino-terminal cleavable presequences as targeting signals. The TIM23 core complex consists of a receptor domain in the intermembrane space and a protein-conducting channel in the inner mitochondrial membrane. TIM23 not only transports water-soluble client proteins to the matrix compartment but also integrates hydrophobic proteins into the inner membrane. We found that membrane insertion of preproteins is regulated by the small TIM23 subunit Mgr2. Site-specific photocrosslinking analysis showed that Mgr2 extensively interacts with different domains of hydrophobic preproteins on their way into the lipid bilayer. Thereby, Mgr2 acts as a lateral gatekeeper of the TIM23 complex and provides a quality control function for the membrane insertion reaction. Loss of Mgr2 prevents the rejection of defective membrane sorting signals in preproteins and interferes with the biogenesis of the mitochondrial fusion machinery leading to fragmentation of the mitochondrial network in cells.
