Lena Böttinger

University of Freiburg, Freiburg, Lower Saxony, Germany

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Publications (8)44.68 Total impact

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    ABSTRACT: The mitochondrial outer membrane contains integral α-helical and β-barrel proteins that are imported from the cytosol. The machineries importing β-barrel proteins have been identified, however, different views exist on the import of α-helical proteins. It has been reported that the biogenesis of Om45, the most abundant signal-anchored protein, does not depend on proteinaceous components, but involves direct insertion into the outer membrane. We show that import of Om45 occurs via the translocase of the outer membrane and the presequence translocase of the inner membrane. Assembly of Om45 in the outer membrane involves the MIM machinery. Om45 thus follows a new mitochondrial biogenesis pathway that uses elements of the presequence import pathway to direct a protein to the outer membrane.
    EMBO Reports 04/2014; · 7.19 Impact Factor
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    ABSTRACT: The formation of the mature cytochrome c oxidase (complex IV) involves the association of nuclear and mitochondria-encoded subunits. The assembly of nuclear-encoded subunits like Cox4 into the mature complex is poorly understood. Cox4 is crucial for the stability of complex IV. To find specific biogenesis factors we analyzed interaction partners of Cox4 by affinity purification and mass spectroscopy. Surprisingly, we identified a complex of Cox4, the mitochondrial Hsp70 (mtHsp70) and its nucleotide-exchange factor Mge1. We generated a yeast mutant of mtHsp70 specifically impaired in the formation of this novel mtHsp70-Mge1-Cox4 complex. Strikingly, the assembly of Cox4 is strongly decreased in these mutant mitochondria. Since Cox4 is a key factor for the biogenesis of complex IV we conclude that the mtHsp70-Mge1-Cox4 complex plays an important role in the formation of cytochrome c oxidase. Cox4 arrests at this chaperone complex in the absence of mature complex IV. Thus, the mtHsp70-Cox4 complex likely serves as a novel delivery system to channel Cox4 into the assembly line when needed.
    Molecular biology of the cell 07/2013; · 5.98 Impact Factor
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    Lena Böttinger, Thomas Becker
    Journal of Molecular Biology 10/2012; · 3.91 Impact Factor
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    ABSTRACT: The inner mitochondrial membrane plays a crucial role in cellular lipid homeostasis through biosynthesis of the non-bilayer forming lipids phosphatidylethanolamine (PE) and cardiolipin (CL). In the yeast Saccharomyces cerevisiae, the majority of cellular PE is synthesized by the mitochondrial phosphatidylserine decarboxylase 1 (Psd1). The biogenesis of Psd1 involves several processing steps. It was speculated that the Psd1 precursor is sorted into the inner membrane and is subsequently released into the intermembrane space by proteolytic removal of a hydrophobic sorting signal. However, components involved in the maturation of the Psd1 precursor have not been identified. We show that processing of Psd1 involves the action of the mitochondrial proteases MPP and Oct1 and an autocatalytic cleavage at a highly conserved LGST motif yielding the α- and β-subunit of the enzyme. The Psd1 β-subunit (Psd1β) forms the membrane anchor, which binds the intermembrane space localized α-subunit (Psd1β). Deletion of a transmembrane segment in the α-subunit results in mislocalization of Psd1 and reduced enzymatic activity. Surprisingly, autocatalytic cleavage does not depend on proper localization to the inner mitochondrial membrane. In summary, membrane integration of Psd1 is crucial for its functionality and for maintenance of mitochondrial lipid homeostasis.
    Journal of Biological Chemistry 09/2012; · 4.65 Impact Factor
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    ABSTRACT: The mitochondrial inner membrane contains two non-bilayer-forming phospholipids, phosphatidylethanolamine (PE) and cardiolipin (CL). Lack of CL leads to destabilization of respiratory chain supercomplexes, a reduced activity of cytochrome c oxidase, and a reduced inner membrane potential Δψ. Although PE is more abundant than CL in the mitochondrial inner membrane, its role in biogenesis and assembly of inner membrane complexes is unknown. We report that similar to the lack of CL, PE depletion resulted in a decrease of Δψ and thus in an impaired import of preproteins into and across the inner membrane. The respiratory capacity and in particular the activity of cytochrome c oxidase were impaired in PE-depleted mitochondria, leading to the decrease of Δψ. In contrast to depletion of CL, depletion of PE did not destabilize respiratory chain supercomplexes but favored the formation of larger supercomplexes (megacomplexes) between the cytochrome bc(1) complex and the cytochrome c oxidase. We conclude that both PE and CL are required for a full activity of the mitochondrial respiratory chain and the efficient generation of the inner membrane potential. The mechanisms, however, are different since these non-bilayer-forming phospholipids exert opposite effects on the stability of respiratory chain supercomplexes.
    Journal of Molecular Biology 09/2012; 423(5):677-86. · 3.91 Impact Factor
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    ABSTRACT: The intermembrane space of mitochondria accommodates the essential mitochondrial intermembrane space assembly (MIA) machinery that catalyzes oxidative folding of proteins. The disulfide bond formation pathway is based on a relay of reactions involving disulfide transfer from the sulfhydryl oxidase Erv1 to Mia40 and from Mia40 to substrate proteins. However, the substrates of the MIA typically contain two disulfide bonds. It was unclear what the mechanisms are that ensure that proteins are released from Mia40 in a fully oxidized form. In this work, we dissect the stage of the oxidative folding relay, in which Mia40 binds to its substrate. We identify dynamics of the Mia40-substrate intermediate complex. Our experiments performed in a native environment, both in organello and in vivo, show that Erv1 directly participates in Mia40-substrate complex dynamics by forming a ternary complex. Thus Mia40 in cooperation with Erv1 promotes the formation of two disulfide bonds in the substrate protein, ensuring the efficiency of oxidative folding in the intermembrane space of mitochondria.
    Molecular biology of the cell 08/2012; 23(20):3957-69. · 5.98 Impact Factor
  • Thomas Becker, Lena Böttinger, Nikolaus Pfanner
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    ABSTRACT: Mitochondria, the powerhouses of the cell, import most of their proteins from the cytosol. It was originally assumed that mitochondria imported precursor proteins via a general pathway but recent studies have revealed a remarkable variety of import pathways and mechanisms. Currently, five different protein import pathways can be distinguished. However, the import machineries cooperate with each other and are connected to other systems that function in the respiratory chain, mitochondrial membrane organization, protein quality control and endoplasmic reticulum-mitochondria junctions. In this Opinion, we propose that mitochondrial protein import should not be seen as an independent task of the organelle and that a network of cooperating machineries is responsible for major mitochondrial functions.
    Trends in Biochemical Sciences 12/2011; 37(3):85-91. · 13.08 Impact Factor
  • Biochimica Et Biophysica Acta-bioenergetics - BBA-BIOENERGETICS. 01/2010; 1797:107-107.