Molecular insights into the m-AAA protease mediated dislocation of transmembrane helices in the mitochondrial inner membrane.

5 years ago

Molecular insights into the m-AAA protease mediated dislocation of transmembrane helices in the mitochondrial inner membrane.

Hyun Kim, Hunsang Lee, Suji Yoo, Seoeun Lee

In the mitochondrial inner membrane, many protein complexes involved in respiration, ATP synthesis, and protein import reside, thus proper regulation of these proteins is essential for cell viability. The mAAA protease, a conserved heterohexameric AAA (ATPases associated with diverse cellular activities) protease composed of the Yta10 and Yta12 proteins, regulates mitochondrial proteostasis by mediating protein maturation and degradation. It also recognizes and mediates dislocation of membrane embedded substrates, including foreign transmembrane (TM) segments, yet the molecular mechanism involved in these processes remains elusive. This study investigated the role of the TM domains in the mAAA protease by systematic replacement of one TM domain at a time in yeast. Our data indicated that replacement of the Yta10 TM2 domain abolishes membrane dislocation for only a subset of substrates, whereas replacement of the Yta12 TM2 domain impairs membrane dislocation for all tested substrates, suggesting different roles of the TM domains in each mAAA protease subunit. Furthermore, mAAA protease mediated membrane dislocation was impaired in the presence of a large downstream hydrophilic moiety in a membrane substrate. This finding suggested that the mAAA protease cannot dislocate large hydrophilic domains across the membrane, indicating that the membrane dislocation probably occurs in a lipid environment. In summary, this study highlights previously underappreciated biological roles of TM domains of the mAAA proteases in mediating recognition and dislocation of membrane embedded substrates.

Publisher URL: http://doi.org/10.1074/jbc.M117.796763

DOI: 10.1074/jbc.M117.796763