title: Cooperation of TOM and TIM23 complexes during translocation of proteins into mitochondria.
abstract: Translocation of the majority of mitochondrial proteins from the cytosol into mitochondria requires the cooperation of TOM and TIM23 complexes in the outer and inner mitochondrial membranes. The molecular mechanisms underlying this cooperation remain largely unknown. Here, we present biochemical and genetic evidence that at least two contacts from the side of the TIM23 complex play an important role in TOM-TIM23 cooperation in vivo. Tim50, likely through its very C-terminal segment, interacts with Tom22. This interaction is stimulated by translocating proteins and is independent of any other TOM-TIM23 contact known so far. Furthermore, the exposure of Tim23 on the mitochondrial surface depends not only on its interaction with Tim50 but also on the dynamics of the TOM complex. Destabilization of the individual contacts reduces the efficiency of import of proteins into mitochondria and destabilization of both contacts simultaneously is not tolerated by yeast cells. We conclude that an intricate and coordinated network of protein-protein interactions involving primarily Tim50 and also Tim23 is required for efficient translocation of proteins across both mitochondrial membranes.
authors.affiliation: Department of Physiological Chemistry, Medical Faculty, University of Munich, Butenandtstrasse 5, 81377 Munich, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Waegemann
authors.affiliation: Department of Physiological Chemistry, Medical Faculty, University of Munich, Butenandtstrasse 5, 81377 Munich, Germany.
authors.forename: Dušan
authors.initials: D
authors.lastname: Popov-Čeleketić
authors.affiliation: Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Neupert
authors.affiliation: Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel.
authors.forename: Abdussalam
authors.initials: A
authors.lastname: Azem
authors.affiliation: Department of Physiological Chemistry, Medical Faculty, University of Munich, Butenandtstrasse 5, 81377 Munich, Germany. Electronic address: dejana.mokranjac@med.uni-muenchen.de.
authors.forename: Dejana
authors.initials: D
authors.lastname: Mokranjac
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D021381:Protein Transport / Q000502:physiology*; D015003:Yeasts / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D005656:Fungal Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins
keywords: TIM23; mitochondria; protein sorting; protein translocation