A novel insertion pathway of mitochondrial outer membrane proteins with multiple transmembrane segments

Hidenori Otera, Yohsuke Taira, Chika Horie, Yurina Suzuki, Hiroyuki Suzuki, Kiyoko Setoguchi, Hiroki Kato, Toshihiko Oka, Katsuyoshi Mihara

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)

Abstract

The central channel Tom40 of the preprotein translocase of outer membrane (TOM) complex is thought to be responsible for the import of virtually all preproteins synthesized outside the mitochondria. In this study, we analyze the topogenesis of the peripheral benzodiazepine receptor (PBR), which integrates into the mitochondrial outer membrane (MOM) through five hydrophobic transmembrane segments (TMSs) and functions in cholesterol import into the inner membrane. Analyses of in vitro and in vivo import into TOM component-depleted mitochondria reveal that PBR import (1) depends on the import receptor Tom70 but requires neither the Tom20 and Tom22 import receptors nor the import channel Tom40, (2) shares the post-Tom70 pathway with the C-tail-anchored proteins, and (3) requires factors of the mitochondrial intermembrane space. Furthermore, membrane integration of mitofusins and mitochondrial ubiquitin ligase, the MOM proteins with two and four TMSs, respectively, proceeds through the same initial pathway. These findings reveal a previously unidentified pathway of the membrane integration of MOM proteins with multiple TMSs.

Original languageEnglish
Pages (from-to)1355-1363
Number of pages9
JournalJournal of Cell Biology
Volume179
Issue number7
DOIs
Publication statusPublished - Dec 31 2007

All Science Journal Classification (ASJC) codes

  • Cell Biology

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