title: Cooperation of stop-transfer and conservative sorting mechanisms in mitochondrial protein transport.
abstract: The mitochondrial inner membrane is a highly protein-rich membrane with central importance for oxidative phosphorylation and metabolite transport. A large number of inner-membrane proteins are synthesized as preproteins with cleavable presequences. Opposing mechanisms of preprotein insertion into the membrane have been debated: stop-transfer with arrest in the inner membrane versus conservative sorting via the matrix. We dissected the membrane insertion of a multispanning ABC transporter. The N-terminal membrane domain was laterally released from the presequence translocase of the inner membrane (TIM23 complex) by a stop-transfer mechanism, whereas the subsequent domain was imported via the matrix heat-shock protein 70 (mtHsp70) motor and exported by the oxidase assembly (OXA) translocase. These observations lead to an unexpected solution to the controversial debate about mitochondrial preprotein sorting. Stop-transfer and conservative sorting are not mutually exclusive pathways but represent sorting mechanisms that cooperate in the membrane integration of a protein with complex topology. We conclude that the multispanning protein is inserted in a modular manner by the coordinated action of two inner-membrane preprotein translocases.
authors.affiliation: Institut für Biochemie und Molekularbiologie, Zentrum für Biochemie und Molekulare Zellforschung (ZBMZ); Fakultät für Biologie, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Bohnert
authors.forename: Peter
authors.initials: P
authors.lastname: Rehling
authors.forename: Bernard
authors.initials: B
authors.lastname: Guiard
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Herrmann
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Pfanner
authors.forename: Martin
authors.initials: M
authors.lastname: van der Laan
mesh_terms: D006868:Hydrolysis; D008928:Mitochondria / Q000378:metabolism*; D021381:Protein Transport