Mitochondrial AAA-ATPase Msp1 detects mislocalized tail-anchored proteins through a dual-recognition mechanism.

ABSTRACT: The conserved AAA-ATPase Msp1 is embedded in the outer mitochondrial membrane and removes mislocalized tail-anchored (TA) proteins upon dysfunction of the guided entry of tail-anchored (GET) pathway. It remains unclear how Msp1 recognizes its substrates. Here, we extensively characterize Msp1 and its substrates, including the mitochondrially targeted Pex15Δ30, and full-length Pex15, which mislocalizes to mitochondria upon dysfunction of Pex19 but not the GET pathway. Moreover, we identify two new substrates, Frt1 and Ysy6. Our results suggest that mislocalized TA proteins expose hydrophobic surfaces in the cytoplasm and are recognized by Msp1 through conserved hydrophobic residues. Introducing a hydrophobic patch into mitochondrial TA proteins transforms them into Msp1 substrates. In addit

SUBMITTER: Li L 

PROVIDER: S-EPMC6446203 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature