SPP 1710:  Dynamik thiolbasierter Redoxschalter in der Zellphysiologie

• Fachliche Zuordnung: Biologie
• Förderung: Förderung von 2014 bis 2023
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 237042534

• Erstellungsjahr: 2022

Zusammenfassung der Projektergebnisse

Das Ziel des Schwerpunktprogramms 1710 war die Erforschung regulatorischer Redox-Modifikationen von Thiolgruppen (sog. „redox switches“), von der molekular-mechanistischen Grundlage bis hin zur Bedeutung im physiologisch-organismischen Kontext. Ein Merkmal war der interdisziplinäre Austausch innerhalb der gesamten Biologie mit einem sehr breiten Spektrum von Modellorganismen und auch angrenzender Disziplinen wie Chemie und Medizin. Dieser breitgefächerte und dennoch integrative Ansatz war möglich, weil die Thiolbasierte Redoxregulation in allen Organismen existiert und methodische Innovationen über die Grenzen von Modellorganismen hinweg ausgetauscht werden können. Während der Laufzeit sind zahlreiche neue (teilweise wegweisende) Werkzeuge und Einsichten entstanden, die sich auch in hochrangigen Publikationen niedergeschlagen haben. Der Schwerpunkt und seine Mitglieder haben eine hohe internationale Sichtbarkeit erreicht. Intensive Networking-Aktivitäten, wenngleich zuletzt wegen Corona eingeschränkt bzw. virtualisiert, haben zu Kollaborationen, Projekten und Publikationen geführt, die ohne den Schwerpunkt nicht zustande gekommen wären. Weiterhin hat der Schwerpunkt zur Ausbildung und Förderung der nächsten Generation von Wissenschaftlern auf diesem Gebiet beigetragen.

Projektbezogene Publikationen (Auswahl)

• Mia40 is a trans-site receptor that drives protein import into the mitochondrial intermembrane space by hydrophobic substrate binding. eLife, 5(c(2016, 6, 25)).
  Peleh, Valentina; Cordat, Emmanuelle & Herrmann, Johannes M
  
• Arylmethylamino steroids as antiparasitic agents. Nature Communications, 8(1).
  Krieg, Reimar; Jortzik, Esther; Goetz, Alice-Anne; Blandin, Stéphanie; Wittlin, Sergio; Elhabiri, Mourad; Rahbari, Mahsa; Nuryyeva, Selbi; Voigt, Kerstin; Dahse, Hans-Martin; Brakhage, Axel; Beckmann, Svenja; Quack, Thomas; Grevelding, Christoph G.; Pinkerton, Anthony B.; Schönecker, Bruno; Burrows, Jeremy; Davioud-Charvet, Elisabeth; Rahlfs, Stefan & Becker, Katja
  
• GRP78 protects a disintegrin and metalloprotease 17 against protein‐disulfide isomerase A6 catalyzed inactivation. FEBS Letters, 591(21), 3567-3587.
  Schäfer, Miriam; Granato, Daniela C.; Krossa, Sebastian; Bartels, Anne‐Kathrin; Yokoo, Sami; Düsterhöft, Stefan; Koudelka, Tomas; Scheidig, Axel J.; Tholey, Andreas; Paes Leme, Adriana F.; Grötzinger, Joachim & Lorenzen, Inken
  
• Real-Time Imaging of the Bacillithiol Redox Potential in the Human PathogenStaphylococcus aureusUsing a Genetically Encoded Bacilliredoxin-Fused Redox Biosensor. Antioxidants & Redox Signaling, 26(15), 835-848.
  Loi, Vu Van; Harms, Manuela; Müller, Marret; Huyen, Nguyen Thi Thu; Hamilton, Chris J.; Hochgräfe, Falko; Pané-Farré, Jan & Antelmann, Haike
  
• The redox‐sensitive module of cyclophilin 20‐3, 2‐cysteine peroxiredoxin and cysteine synthase integrates sulfur metabolism and oxylipin signaling in the high light acclimation response. The Plant Journal, 91(6), 995-1014.
  Müller, Sara M.; Wang, Shanshan; Telman, Wilena; Liebthal, Michael; Schnitzer, Helena; Viehhauser, Andrea; Sticht, Carsten; Delatorre, Carolina; Wirtz, Markus; Hell, Rüdiger & Dietz, Karl‐Josef
  
• Thioredoxin and NADPH-Dependent Thioredoxin Reductase C Regulation of Tetrapyrrole Biosynthesis. Plant Physiology, 175(2), 652-666.
  Da, Qingen; Wang, Peng; Wang, Menglong; Sun, Ting; Jin, Honglei; Liu, Bing; Wang, Jinfa; Grimm, Bernhard & Wang, Hong-Bin
  
• Electrochemical Quantification of Extracellular Local H2O2Kinetics Originating from Single Cells. Antioxidants & Redox Signaling, 29(6), 501-517.
  Bozem, Monika; Knapp, Phillip; Mirčeski, Valentin; Slowik, Ewa J.; Bogeski, Ivan; Kappl, Reinhard; Heinemann, Christian & Hoth, Markus
  
• N-Acetyl Cysteine Functions as a Fast-Acting Antioxidant by Triggering Intracellular H2S and Sulfane Sulfur Production. Cell Chemical Biology, 25(4), 447-459.e4.
  Ezeriņa, Daria; Takano, Yoko; Hanaoka, Kenjiro; Urano, Yasuteru & Dick, Tobias P.
  
• Neutrophil-generated HOCl leads to non-specific thiol oxidation in phagocytized bacteria. eLife, 7(c(2018, 3, 6)).
  Degrossoli, Adriana; Müller, Alexandra; Xie, Kaibo; Schneider, Jannis F; Bader, Verian; Winklhofer, Konstanze F; Meyer, Andreas J & Leichert, Lars I
  
• On the Effects of Reactive Oxygen Species and Nitric Oxide on Red Blood Cell Deformability. Frontiers in Physiology, 9(c(2018, 5, 11)).
  Diederich, Lukas; Suvorava, Tatsiana; Sansone, Roberto; Keller, T. C. Stevenson; Barbarino, Frederik; Sutton, Thomas R.; Kramer, Christian M.; Lückstädt, Wiebke; Isakson, Brant E.; Gohlke, Holger; Feelisch, Martin; Kelm, Malte & Cortese-Krott, Miriam M.
  
• ProteinS-Bacillithiolation Functions in Thiol Protection and Redox Regulation of the Glyceraldehyde-3-Phosphate Dehydrogenase Gap inStaphylococcus aureusUnder Hypochlorite Stress. Antioxidants & Redox Signaling, 28(6), 410-430.
  Imber, Marcel; Huyen, Nguyen Thi Thu; Pietrzyk-Brzezinska, Agnieszka J.; Loi, Vu Van; Hillion, Melanie; Bernhardt, Jörg; Thärichen, Lena; Kolšek, Katra; Saleh, Malek; Hamilton, Chris J.; Adrian, Lorenz; Gräter, Frauke; Wahl, Markus C. & Antelmann, Haike
  
• Redox-sensitive GFP fusions for monitoring the catalytic mechanism and inactivation of peroxiredoxins in living cells. Redox Biology, 14(c(2018, 4)), 549-556.
  Staudacher, Verena; Trujillo, Madia; Diederichs, Tim; Dick, Tobias P.; Radi, Rafael; Morgan, Bruce & Deponte, Marcel
  
• Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis. Cell, 172(3), 409-422.e21.
  Ingold, Irina; Berndt, Carsten; Schmitt, Sabine; Doll, Sebastian; Poschmann, Gereon; Buday, Katalin; Roveri, Antonella; Peng, Xiaoxiao; Porto Freitas, Florencio; Seibt, Tobias; Mehr, Lisa; Aichler, Michaela; Walch, Axel; Lamp, Daniel; Jastroch, Martin; Miyamoto, Sayuri; Wurst, Wolfgang; Ursini, Fulvio; Arnér, Elias S.J.; ... & Conrad, Marcus
  
• The chloroplast 2-cysteine peroxiredoxin functions as thioredoxin oxidase in redox regulation of chloroplast metabolism. eLife, 7(c(2018, 10, 12)).
  Vaseghi, Mohamad-Javad; Chibani, Kamel; Telman, Wilena; Liebthal, Michael Florian; Gerken, Melanie; Schnitzer, Helena; Mueller, Sara Mareike & Dietz, Karl-Josef
  
• Towards Initial Indications for a Thiol-Based Redox Control of Arabidopsis 5-Aminolevulinic Acid Dehydratase. Antioxidants, 7(11), 152.
  Wittmann, Daniel; Kløve, Sigri; Wang, Peng & Grimm, Bernhard
  
• An essential thioredoxin-type protein of Trypanosoma brucei acts as redox-regulated mitochondrial chaperone. PLOS Pathogens, 15(9), e1008065.
  Currier, Rachel B.; Ulrich, Kathrin; Leroux, Alejandro E.; Dirdjaja, Natalie; Deambrosi, Matías; Bonilla, Mariana; Ahmed, Yasar Luqman; Adrian, Lorenz; Antelmann, Haike; Jakob, Ursula; Comini, Marcelo A. & Krauth-Siegel, R. Luise
  
• Hyperoxidation of mitochondrial peroxiredoxin limits H 2 O 2 ‐induced cell death in yeast. The EMBO Journal, 38(18).
  Calabrese, Gaetano; Peker, Esra; Amponsah, Prince Saforo; Hoehne, Michaela Nicole; Riemer, Trine; Mai, Marie; Bienert, Gerd Patrick; Deponte, Marcel; Morgan, Bruce & Riemer, Jan
  
• KDEL Receptor 1 Contributes to Cell Surface Association of Protein Disulfide Isomerases. Cellular Physiology and Biochemistry, 52(4), 580-868.
  Bartels AK; Göttert S; Desel C; Schäfer M; Krossa S; Scheidig AJ; Grötzinger J & Lorenzen I
  
• MpTCP1 controls cell proliferation and redox processes in Marchantia polymorpha. New Phytologist, 224(4), 1627-1641.
  Busch, Andrea; Deckena, Marek; Almeida‐Trapp, Marilia; Kopischke, Sarah; Kock, Cilian; Schüssler, Esther; Tsiantis, Miltos; Mithöfer, Axel & Zachgo, Sabine
  
• Nano-Sampling and Reporter Tools to Study Metabolic Regulation in Zebrafish. Frontiers in Cell and Developmental Biology, 7(c(2019, 2, 19)).
  Dickmeis, Thomas; Feng, Yi; Mione, Maria Caterina; Ninov, Nikolay; Santoro, Massimo; Spaink, Herman P. & Gut, Philipp
  
• Quantifying changes in the bacterial thiol redox proteome during host-pathogen interaction. Redox Biology, 21(c(2019, 2)), 101087.
  Xie, Kaibo; Bunse, Christina; Marcus, Katrin & Leichert, Lars I.
  
• Redox-mediated kick-start of mitochondrial energy metabolism drives resource-efficient seed germination. Proceedings of the National Academy of Sciences, 117(1), 741-751.
  Nietzel, Thomas; Mostertz, Jörg; Ruberti, Cristina; Née, Guillaume; Fuchs, Philippe; Wagner, Stephan; Moseler, Anna; Müller-Schüssele, Stefanie J.; Benamar, Abdelilah; Poschet, Gernot; Büttner, Michael; Møller, Ian Max; Lillig, Christopher H.; Macherel, David; Wirtz, Markus; Hell, Rüdiger; Finkemeier, Iris; Meyer, Andreas J.; Hochgräfe, Falko & Schwarzländer, Markus
  
• The Charcot–Marie Tooth Disease Mutation R94Q in MFN2 Decreases ATP Production but Increases Mitochondrial Respiration under Conditions of Mild Oxidative Stress. Cells, 8(10), 1289.
  Wolf, Christina; Zimmermann, Rahel; Thaher, Osamah; Bueno, Diones; Wüllner, Verena; Schäfer, Michael K.E.; Albrecht, Philipp & Methner, Axel
  
• A tryparedoxin-coupled biosensor reveals a mitochondrial trypanothione metabolism in trypanosomes. eLife, 9(c(2020, 1, 31)).
  Ebersoll, Samantha; Bogacz, Marta; Günter, Lina M; Dick, Tobias P & Krauth-Siegel, R Luise
  
• Dual‐color 3D‐dSTORM colocalization and quantification of ROXY1 and RNAPII variants throughout the transcription cycle in root meristem nuclei. The Plant Journal, 104(5), 1423-1436.
  Maß, Lucia; Holtmannspötter, Michael & Zachgo, Sabine
  
• Extracellular Redox Regulation of α7β Integrin-Mediated Cell Migration Is Signaled via a Dominant Thiol-Switch. Antioxidants, 9(3), 227.
  Bergerhausen, Lukas; Grosche, Julius; Meißner, Juliane; Hecker, Christina; Caliandro, Michele F.; Westerhausen, Christoph; Kamenac, Andrej; Rezaei, Maryam; Mörgelin, Matthias; Poschmann, Gereon; Vestweber, Dietmar; Hanschmann, Eva-Maria & Eble, Johannes A.
  
• Genetically encoded thiol redox-sensors in the zebrafish model: lessons for embryonic development and regeneration. Biological Chemistry, 402(3), 363-378.
  Breus, Oksana & Dickmeis, Thomas
  
• In Vivo NADH/NAD+ Biosensing Reveals the Dynamics of Cytosolic Redox Metabolism in Plants. The Plant Cell, 32(10), 3324-3345.
  Steinbeck, Janina; Fuchs, Philippe; Negroni, Yuri L.; Elsässer, Marlene; Lichtenauer, Sophie; Stockdreher, Yvonne; Feitosa-Araujo, Elias; Kroll, Johanna B.; Niemeier, Jan-Ole; Humberg, Christoph; Smith, Edward N.; Mai, Marie; Nunes-Nesi, Adriano; Meyer, Andreas J.; Zottini, Michela; Morgan, Bruce; Wagner, Stephan & Schwarzländer, Markus
  
• Mitochondrial [4Fe-4S] protein assembly involves reductive [2Fe-2S] cluster fusion on ISCA1–ISCA2 by electron flow from ferredoxin FDX2. Proceedings of the National Academy of Sciences, 117(34), 20555-20565.
  Weiler, Benjamin Dennis; Brück, Marie-Christin; Kothe, Isabell; Bill, Eckhard; Lill, Roland & Mühlenhoff, Ulrich
  
• Molecular basis for the distinct functions of redox-active and FeS-transfering glutaredoxins. Nature Communications, 11(1).
  Trnka, Daniel; Engelke, Anna D.; Gellert, Manuela; Moseler, Anna; Hossain, Md Faruq; Lindenberg, Tobias T.; Pedroletti, Luca; Odermatt, Benjamin; de Souza, João V.; Bronowska, Agnieszka K.; Dick, Tobias P.; Mühlenhoff, Uli; Meyer, Andreas J.; Berndt, Carsten & Lillig, Christopher Horst
  
• Oxidative Stress-Induced STIM2 Cysteine Modifications Suppress Store-Operated Calcium Entry. Cell Reports, 33(3), 108292.
  Gibhardt, Christine Silvia; Cappello, Sabrina; Bhardwaj, Rajesh; Schober, Romana; Kirsch, Sonja Agnes; Bonilla del Rio, Zuriñe; Gahbauer, Stefan; Bochicchio, Anna; Sumanska, Magdalena; Ickes, Christian; Stejerean-Todoran, Ioana; Mitkovski, Miso; Alansary, Dalia; Zhang, Xin; Revazian, Aram; Fahrner, Marc; Lunz, Victoria; Frischauf, Irene; Luo, Ting; ... & Bogeski, Ivan
  
• Proteasomal degradation induced by DPP9‐mediated processing competes with mitochondrial protein import. The EMBO Journal, 39(19).
  Finger, Yannik; Habich, Markus; Gerlich, Sarah; Urbanczyk, Sophia; van de Logt, Erik; Koch, Julian; Schu, Laura; Lapacz, Kim Jasmin; Ali, Muna; Petrungaro, Carmelina; Salscheider, Silja Lucia; Pichlo, Christian; Baumann, Ulrich; Mielenz, Dirk; Dengjel, Joern; Brachvogel, Bent; Hofmann, Kay & Riemer, Jan
  
• Quantitative assessment of the determinant structural differences between redox-active and inactive glutaredoxins. Nature Communications, 11(1).
  Liedgens, Linda; Zimmermann, Jannik; Wäschenbach, Lucas; Geissel, Fabian; Laporte, Hugo; Gohlke, Holger; Morgan, Bruce & Deponte, Marcel
  
• Quantitative assessment of the determinant structural differences between redox-active and inactive glutaredoxins. Nature Communications, 11(1).
  Liedgens, Linda; Zimmermann, Jannik; Wäschenbach, Lucas; Geissel, Fabian; Laporte, Hugo; Gohlke, Holger; Morgan, Bruce & Deponte, Marcel
  
• Real-time monitoring of peroxiredoxin oligomerization dynamics in living cells. Proceedings of the National Academy of Sciences, 117(28), 16313-16323.
  Pastor-Flores, Daniel; Talwar, Deepti; Pedre, Brandán & Dick, Tobias P.
  
• Thiol-based switching mechanisms of stress-sensing chaperones. Biological Chemistry, 402(3), 239-252.
  Ulrich, Kathrin; Schwappach, Blanche & Jakob, Ursula
  
• Chloroplast-derived photo-oxidative stress causes changes in H2O2 and EGSH in other subcellular compartments. Plant Physiology, 186(1), 125-141.
  Ugalde, José Manuel; Fuchs, Philippe; Nietzel, Thomas; Cutolo, Edoardo A; Homagk, Maria; Vothknecht, Ute C; Holuigue, Loreto; Schwarzländer, Markus; Müller-Schüssele, Stefanie J & Meyer, Andreas J
  
• Increased levels of mitochondrial import factor Mia40 prevent the aggregation of polyQ proteins in the cytosol. The EMBO Journal, 40(16).
  Schlagowski, Anna M; Knöringer, Katharina; Morlot, Sandrine; Sánchez Vicente, Ana; Flohr, Tamara; Krämer, Lena; Boos, Felix; Khalid, Nabeel; Ahmed, Sheraz; Schramm, Jana; Murschall, Lena M; Haberkant, Per; Stein, Frank; Riemer, Jan; Westermann, Benedikt; Braun, Ralf J; Winklhofer, Konstanze F; Charvin, Gilles & Herrmann, Johannes M
  
• Molecular Basis for the Interactions of Human Thioredoxins with Their Respective Reductases. Oxidative Medicine and Cellular Longevity, 2021(1).
  Hossain, Md Faruq; Bodnar, Yana; Klein, Calvin; Salas, Clara Ortegón; Arnér, Elias S. J.; Gellert, Manuela & Lillig, Christopher Horst
  
• N-terminal tyrosine of ISCU2 triggers [2Fe-2S] cluster synthesis by ISCU2 dimerization. Nature Communications, 12(1).
  Freibert, Sven-A.; Boniecki, Michal T.; Stümpfig, Claudia; Schulz, Vinzent; Krapoth, Nils; Winge, Dennis R.; Mühlenhoff, Ulrich; Stehling, Oliver; Cygler, Miroslaw & Lill, Roland
  
• Peroxiredoxins couple metabolism and cell division in an ultradian cycle. Nature Chemical Biology, 17(4), 477-484.
  Amponsah, Prince Saforo; Yahya, Galal; Zimmermann, Jannik; Mai, Marie; Mergel, Sarah; Mühlhaus, Timo; Storchova, Zuzana & Morgan, Bruce
  
• Red Blood Cell and Endothelial eNOS Independently Regulate Circulating Nitric Oxide Metabolites and Blood Pressure. Circulation, 144(11), 870-889.
  Leo, Francesca; Suvorava, Tatsiana; Heuser, Sophia K.; Li, Junjie; LoBue, Anthea; Barbarino, Frederik; Piragine, Eugenia; Schneckmann, Rebekka; Hutzler, Beate; Good, Miranda E.; Fernandez, Bernadette O.; Vornholz, Lukas; Rogers, Stephen; Doctor, Allan; Grandoch, Maria; Stegbauer, Johannes; Weitzberg, Eddie; Feelisch, Martin; Lundberg, Jon O.; ... & Cortese-Krott, Miriam M.
  
• Redox proteomics reveals an interdependence of redox modification and location of adhesome proteins in NGF-treated PC12 cells. Free Radical Biology and Medicine, 164(c(2021, 2)), 341-353.
  Meißner, Juliane; Rezaei, Maryam; Siepe, Isabel; Ackermann, Doreen; König, Simone & Eble, Johannes A.
  
• Endoplasmic reticulum oxidoreductin provides resilience against reductive stress and hypoxic conditions by mediating luminal redox dynamics. The Plant Cell, 34(10), 4007-4027.
  Ugalde, José Manuel; Aller, Isabel; Kudrjasova, Lika; Schmidt, Romy R; Schlößer, Michelle; Homagk, Maria; Fuchs, Philippe; Lichtenauer, Sophie; Schwarzländer, Markus; Müller-Schüssele, Stefanie J & Meyer, Andreas J
  
• GDAP1 loss of function inhibits the mitochondrial pyruvate dehydrogenase complex by altering the actin cytoskeleton. Communications Biology, 5(1).
  Wolf, Christina; Pouya, Alireza; Bitar, Sara; Pfeiffer, Annika; Bueno, Diones; Rojas-Charry, Liliana; Arndt, Sabine; Gomez-Zepeda, David; Tenzer, Stefan; Bello, Federica Dal; Vianello, Caterina; Ritz, Sandra; Schwirz, Jonas; Dobrindt, Kristina; Peitz, Michael; Hanschmann, Eva-Maria; Mencke, Pauline; Boussaad, Ibrahim; Silies, Marion; ... & Methner, Axel
  
• Glutaredoxin 2 promotes SP-1-dependent CSPG4 transcription and migration of wound healing NG2 glia and glioma cells: Enzymatic Taoism. Redox Biology, 49(c(2022, 2)), 102221.
  Wilms, Christina; Lepka, Klaudia; Häberlein, Felix; Edwards, Steven; Felsberg, Jörg; Pudelko, Linda; Lindenberg, Tobias T.; Poschmann, Gereon; Qin, Nan; Volbracht, Katrin; Prozorovski, Tim; Meuth, Sven G.; Kahlert, Ulf D.; Remke, Marc; Aktas, Orhan; Reifenberger, Guido; Bräutigam, Lars; Odermatt, Benjamin & Berndt, Carsten
  
• Structure and Function of Redox-Sensitive Superfolder Green Fluorescent Protein Variant. Antioxidants & Redox Signaling, 37(1-3), 1-18.
  Heimsch, Kim C.; Gertzen, Christoph G.W.; Schuh, Anna Katharina; Nietzel, Thomas; Rahlfs, Stefan; Przyborski, Jude M.; Gohlke, Holger; Schwarzländer, Markus; Becker, Katja & Fritz-Wolf, Karin