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Nils Wiedemann  - - - 
Top co-authors See all
Nikolaus Pfanner

244 shared publications

Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany

Paul Schanda

79 shared publications

Institut de Biologie Structurale, Univ. Grenoble Alpes, CEA, CNRS, IBS

Bettina Warscheid

48 shared publications

BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg 79104, Germany

Stefan Günther

48 shared publications

Institute of Pharmaceutical SciencesAlbert-Ludwigs-Universität Freiburg Hermann-Herder-Str. 9 79104 Freiburg Germany

Bernd Kammerer

16 shared publications

Center for Biological Systems Analysis, ZBSA, Albert-Ludwigs-University Freiburg, Freiburg, Germany

Publication Record
Distribution of Articles published per year 
(2001 - 2018)
Total number of journals
published in
Publications See all
Article 0 Reads 0 Citations Structural Basis of Membrane Protein Chaperoning through the Mitochondrial Intermembrane Space. Katharina Weinhäupl, Caroline Lindau, Audrey Hessel, Yong Wa... Published: 15 November 2018
Cell, doi: 10.1016/j.cell.2018.10.039
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
The exchange of metabolites between the mitochondrial matrix and the cytosol depends on β-barrel channels in the outer membrane and α-helical carrier proteins in the inner membrane. The essential translocase of the inner membrane (TIM) chaperones escort these proteins through the intermembrane space, but the structural and mechanistic details remain elusive. We have used an integrated structural biology approach to reveal the functional principle of TIM chaperones. Multiple clamp-like binding sites hold the mitochondrial membrane proteins in a translocation-competent elongated form, thus mimicking characteristics of co-translational membrane insertion. The bound preprotein undergoes conformational dynamics within the chaperone binding clefts, pointing to a multitude of dynamic local binding events. Mutations in these binding sites cause cell death or growth defects associated with impairment of carrier and β-barrel protein biogenesis. Our work reveals how a single mitochondrial "transfer-chaperone" system is able to guide α-helical and β-barrel membrane proteins in a "nascent chain-like" conformation through a ribosome-free compartment.
Article 0 Reads 1 Citation Complete Native Stable Isotope Labeling by Amino Acids of Saccharomyces cerevisiae for Global Proteomic Analysis Stefan Dannenmaier, Sebastian B. Stiller, Marcel Morgenstern... Published: 13 August 2018
Analytical Chemistry, doi: 10.1021/acs.analchem.8b02557
DOI See at publisher website PubMed View at PubMed
Article 6 Reads 0 Citations Metabolic profiling of isolated mitochondria and cytoplasm reveals compartment-specific metabolic responses Daqiang Pan, Caroline Lindau, Simon Lagies, Nils Wiedemann, ... Published: 31 March 2018
Metabolomics, doi: 10.1007/s11306-018-1352-x
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
Subcellular compartmentalization enables eukaryotic cells to carry out different reactions at the same time, resulting in different metabolite pools in the subcellular compartments. Thus, mutations affecting the mitochondrial energy metabolism could cause different metabolic alterations in mitochondria compared to the cytoplasm. Given that the metabolite pool in the cytosol is larger than that of other subcellular compartments, metabolic profiling of total cells could miss these compartment-specific metabolic alterations. To reveal compartment-specific metabolic differences, mitochondria and the cytoplasmic fraction of baker’s yeast Saccharomyces cerevisiae were isolated and subjected to metabolic profiling. Mitochondria were isolated through differential centrifugation and were analyzed together with the remaining cytoplasm by gas chromatography–mass spectrometry (GC–MS) based metabolic profiling. Seventy-two metabolites were identified, of which eight were found exclusively in mitochondria and sixteen exclusively in the cytoplasm. Based on the metabolic signature of mitochondria and of the cytoplasm, mutants of the succinate dehydrogenase (respiratory chain complex II) and of the FOF1-ATP-synthase (complex V) can be discriminated in both compartments by principal component analysis from wild-type and each other. These mitochondrial oxidative phosphorylation machinery mutants altered not only citric acid cycle related metabolites but also amino acids, fatty acids, purine and pyrimidine intermediates and others. By applying metabolomics to isolated mitochondria and the corresponding cytoplasm, compartment-specific metabolic signatures can be identified. This subcellular metabolomics analysis is a powerful tool to study the molecular mechanism of compartment-specific metabolic homeostasis in response to mutations affecting the mitochondrial metabolism. The online version of this article (10.1007/s11306-018-1352-x) contains supplementary material, which is available to authorized users.
Article 5 Reads 11 Citations Membrane protein insertion through a mitochondrial β-barrel gate Alexandra I. C. Höhr, Caroline Lindau, Christophe Wirth, Jia... Published: 18 January 2018
Science, doi: 10.1126/science.aah6834
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The biogenesis of mitochondria, chloroplasts and Gram-negative bacteria requires insertion of β-barrel proteins into the outer membranes. Homologous Omp85 proteins are essential for membrane insertion of β-barrel precursors. It is unknown if precursors are threaded through the channel interior and exit laterally or if they are translocated into the membrane at the Omp85-lipid interface. We have mapped the interaction of a precursor in transit with the mitochondrial Omp85 channel Sam50 in the native membrane environment. The precursor is translocated into the channel interior, interacts with an internal loop and inserts into the lateral gate by β-signal exchange. Transport through the Omp85 channel interior followed by release through the lateral gate into the lipid phase may represent a basic mechanism for membrane insertion of β-barrel proteins.
PROCEEDINGS-ARTICLE 25 Reads 0 Citations Mitochondrial metabolomics reveals compartment-specific metabolic responses in yeast cells Bernd Kammerer, Daqiang Pan, Caroline Lindau, Simon Lagies, ... Published: 20 November 2017
Proceedings of The 2nd International Electronic Conference on Metabolomics, doi: 10.3390/iecm-2-04981
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Mutations in mitochondrial membrane proteins could cause physiological and metabolic alterations in mitochondria as well as in cytosol. In order to address the origin of these alterations, mitochondria and cytosol of yeast wild-type BY4741 and two mutants, sdh2Δ and atp4Δ, were isolated from whole cells. These three compartments, namely mitochondria, cytosol and whole cell, were analyzed by gas chromatography-mass spectrometry based metabolic profiling, identifying seventy-three metabolites altogether, from which sixteen or ten were not detected either in mitochondria or cytosol. Compartment-specific distribution and regulation of metabolites were observed, showing the responses to the deletions of sdh2 and atp4. Based on the metabolic signature in mitochondrial matrix and cytosol, both mutants can be discriminated from wild-type by principal component analysis. De letions of electron chain transport components, sdh2 and atp4, altered not only citrate cycle related metabolites, but also diverse metabolites including amino acids, fatty acids, purine and pyrimidine intermediates and others. By applying metabolomics to isolated mitochondria and cytosol, compartment-specific metabolic regulation can be identified, which is helpful in understanding the molecular mechanism of mitochondrial homeostasis in response to genetic mutations.
Article 0 Reads 28 Citations Definition of a High-Confidence Mitochondrial Proteome at Quantitative Scale Marcel Morgenstern, Sebastian B. Stiller, Philipp Lübbert, C... Published: 27 June 2017
Cell Reports, doi: 10.1016/j.celrep.2017.06.014
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Mitochondria perform central functions in cellular bioenergetics, metabolism, and signaling, and their dysfunction has been linked to numerous diseases. The available studies cover only part of the mitochondrial proteome, and a separation of core mitochondrial proteins from associated fractions has not been achieved. We developed an integrative experimental approach to define the proteome of east mitochondria. We classified > 3,300 proteins of mitochondria and mitochondria-associated fractions and defined 901 high-confidence mitochondrial proteins, expanding the set of mitochondrial proteins by 82. Our analysis includes protein abundance under fermentable and nonfermentable growth, submitochondrial localization, single-protein experiments, and subcellular classification of mitochondria-associated fractions. We identified mitochondrial interactors of respiratory chain supercomplexes, ATP synthase, AAA proteases, the mitochondrial contact site and cristae organizing system (MICOS), and the coenzyme Q biosynthesis cluster, as well as mitochondrial proteins with dual cellular localization. The integrative proteome provides a high-confidence source for the characterization of physiological and pathophysiological functions of mitochondria and their integration into the cellular environment.