Clearing tail-anchored proteins from mitochondria

22.05.2014

Opali?ski L, Becker T, Pfanner N.

Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):7888-9

Proc Natl Acad Sci U S A.         online article

Proteins with a C-terminal transmembrane domain (tail-anchored) fulfill a plethora of crucial functions in the eukaryotic cell. The targeting of the tail-anchored precursor proteins to the endoplasmic reticulum involves cytosolic and membrane-bound factors of the guided entry of tail-anchored (GET) machinery. Defects in this targeting system leads to mislocalization to the mitochondrial outer membrane. So far, it was not understood how the mitochondria deal with these proteins.  A recent study addressed this issue using the model substrate Pex15. Pex15 is a tail-anchored protein  that is targeted via the GET machinery to the endoplasmic reticulum and is subsequently sorted via vesicular trafficking to peroxisomes. Upon defects in the GET machinery Pex15 is mislocalized to the mitochondrial outer membrane. The conserved AAA-ATPase Msp1 of the mitochondrial outer membrane removes mistargeted Pex15 and stimulates its turnover. Thus, Msp1 represents a novel molecular factor to control targeting of proteins within the cell.