title: The role of mitochondria and the CIA machinery in the maturation of cytosolic and nuclear iron-sulfur proteins.
abstract: Mitochondria have been derived from alpha-bacterial endosymbionts during the evolution of eukaryotes. Numerous bacterial functions have been maintained inside the organelles including fatty acid degradation, citric acid cycle, oxidative phosphorylation, and the synthesis of heme or lipoic acid cofactors. Additionally, mitochondria have inherited the bacterial iron-sulfur cluster assembly (ISC) machinery. Many of the ISC components are essential for cell viability because they generate a still unknown, sulfur-containing compound for the assembly of cytosolic and nuclear Fe/S proteins that perform important functions in, e.g., protein translation, DNA synthesis and repair, and chromosome segregation. The sulfur-containing compound is exported by the mitochondrial ABC transporter Atm1 (human ABCB7) and utilized by components of the cytosolic iron-sulfur protein assembly (CIA) machinery. An appealing minimal model for the striking compartmentation of eukaryotic Fe/S protein biogenesis is provided by organisms that contain mitosomes instead of mitochondria. Mitosomes have been derived from mitochondria by reductive evolution, during which they have lost virtually all classical mitochondrial tasks. Nevertheless, mitosomes harbor all core ISC components which presumably have been maintained for assisting the maturation of cytosolic-nuclear Fe/S proteins. The current review is centered around the Atm1 export process. We present an overview on the mitochondrial requirements for the export reaction, summarize recent insights into the 3D structure and potential mechanism of Atm1, and explain how the CIA machinery uses the mitochondrial export product for the assembly of cytosolic and nuclear Fe/S proteins.
authors.affiliation: Institut für Zytobiologie, Philipps-Universität Marburg, Robert-Koch-Str. 6, 35032 Marburg, Germany; LOEWE Zentrum für Synthetische Mikrobiologie SynMikro, Hans-Meerwein-Str. 6, 35043 Marburg, Germany. Electronic address: Lill@staff.uni-marburg.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Lill
authors.affiliation: Institut für Zytobiologie, Philipps-Universität Marburg, Robert-Koch-Str. 6, 35032 Marburg, Germany; Department of Molecular and Cellular Biology, Faculty of Biotechnology, University of Gdansk, 80-822 Gdansk, Poland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Dutkiewicz
authors.affiliation: Institut für Zytobiologie, Philipps-Universität Marburg, Robert-Koch-Str. 6, 35032 Marburg, Germany; LOEWE Zentrum für Synthetische Mikrobiologie SynMikro, Hans-Meerwein-Str. 6, 35043 Marburg, Germany.
authors.forename: Sven A
authors.initials: SA
authors.lastname: Freibert
authors.affiliation: Institut für Zytobiologie, Philipps-Universität Marburg, Robert-Koch-Str. 6, 35032 Marburg, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Heidenreich
authors.affiliation: Institut für Zytobiologie, Philipps-Universität Marburg, Robert-Koch-Str. 6, 35032 Marburg, Germany; LOEWE Zentrum für Synthetische Mikrobiologie SynMikro, Hans-Meerwein-Str. 6, 35043 Marburg, Germany.
authors.forename: Judita
authors.initials: J
authors.lastname: Mascarenhas
authors.affiliation: Institut für Zytobiologie, Philipps-Universität Marburg, Robert-Koch-Str. 6, 35032 Marburg, Germany.
authors.forename: Daili J
authors.initials: DJ
authors.lastname: Netz
authors.affiliation: Institut für Zytobiologie, Philipps-Universität Marburg, Robert-Koch-Str. 6, 35032 Marburg, Germany.
authors.forename: Viktoria D
authors.initials: VD
authors.lastname: Paul
authors.affiliation: Institut für Zytobiologie, Philipps-Universität Marburg, Robert-Koch-Str. 6, 35032 Marburg, Germany; Fachbereich Chemie, TU Kaiserslautern, Erwin-Schrödinger-Straße 54, 67663 Kaiserslautern, Germany.
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Pierik
authors.affiliation: Institut für Zytobiologie, Philipps-Universität Marburg, Robert-Koch-Str. 6, 35032 Marburg, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Richter
authors.affiliation: Institut für Zytobiologie, Philipps-Universität Marburg, Robert-Koch-Str. 6, 35032 Marburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Stümpfig
authors.affiliation: Institut für Zytobiologie, Philipps-Universität Marburg, Robert-Koch-Str. 6, 35032 Marburg, Germany; LOEWE Zentrum für Synthetische Mikrobiologie SynMikro, Hans-Meerwein-Str. 6, 35043 Marburg, Germany.
authors.forename: Vasundara
authors.initials: V
authors.lastname: Srinivasan
authors.affiliation: Institut für Zytobiologie, Philipps-Universität Marburg, Robert-Koch-Str. 6, 35032 Marburg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Stehling
authors.affiliation: Institut für Zytobiologie, Philipps-Universität Marburg, Robert-Koch-Str. 6, 35032 Marburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mühlenhoff
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology
chemical_list: C113037:ABCB7 protein, human; D018528:ATP-Binding Cassette Transporters; D007506:Iron-Sulfur Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins
keywords: ABC transporter; Atm1–ABCB7; Cysteine desulfurase; Frataxin; Glutaredoxin; Glutathione; Iron storage disease; Iron–sulfur cluster; Membrane transport