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Articles by Werner Schmitz
HMOX1 controls a heme-ferritin switch that protects cells from ferroptosis
Abstract INTRODUCTION RESULTS DISCUSSION MATERIALS AND METHODS Acknowledgments Supplementary Materials REFERENCES Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Modulating the intracellular labile iron pool (LIP) has emerged as a promising strategy to induce ferroptosis in cancer cells, offering a way to overcome resistance to apoptosis-based therapies.
Metabolic rewiring driven by phosphoglycolate phosphatase deletion inhibits ferroptosis
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Abstract INTRODUCTION RESULTS DISCUSSION MATERIALS AND METHODS Acknowledgments Supplementary Materials REFERENCES Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Modulating ferroptosis, a form of cell death driven by uncontrolled lipid peroxidation, is of interest in numerous diseases. Here, we found that the deletion of phosphoglycolate phosphatase (PGP), an essential enzyme that safeguards high glycolytic flux, suppresses ferroptosis.
By Xiao Yu, Fan Xia, Bolan Gan, Marian Brenner, Sina Höhlein, Paul J. Wirth, Leon Neidt, Melina Lappe, Elisa Hopke, Eirini Sfakianaki, Martina Fischer, Kerstin Hadamek, Angelika Keller, Sebastian Bothe, Anna M Schmoker, Arminja N. Kettenbach, Agnes Fekete, Ágnes A Fekete, Werner Schmitz, Ingrid Tessmer, Elisabeth Jeanclos, Antje Gohla
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Science Magazine
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Author Correction: 7-Dehydrocholesterol is an endogenous suppressor of ferroptosis
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Correction to: Nature https://doi.org/10.1038/s41586-023-06878-9 Published online 31 January 2024 In the originally published version of this article, the blank values in Extended Data Fig. 2a,b correspond to background fluorescence measurements of a stable commercial resazurin solution (AquaBluer Cell Viability Assay Solution, Multi-Target Pharmaceuticals, cat. no. 6015), diluted in complete culture medium.
By Florencio Porto Freitas, Hamed Alborzinia, Palina Nepachalovich, Lohans Pedrera, Omkar Zilka, Alex Inague, Corinna Klein, Nesrine Aroua, Kamini Kaushal, Bettina Kast, Svenja Lorenz Verified, Zhiyi Chen, Sena Atici, Sebastian Doll, Emily Schaefer, Werner Schmitz, Peter Imming, Sayuri Miyamoto, Ann M. Wehman, Karoly Mirnics, Lokender Kumar, Judith Klein-Seetharaman, Svenja Meierjohann, Isabel Weigand, Matthias Kroiss, Georg W. Bornkamm, Fernando Gomes, Manjima B Sathian, David B. Konrad, Douglas Covey, Bernhard Michalke, Kurt Bommert, Ralf Bargou, Ana J. García-Sáez, Derek Pratt, Maria Fedorova, Andreas Trumpp, Marcus Conrad, Viktoria Kunz, Helene Nehring, Ifedapo Ekpo, Aline Horling, Thiago C. Genaro-Mattos
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Nature
Verified
Riboflavin metabolism shapes FSP1-driven ferroptosis resistance
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Abstract Membrane protection against oxidative insults is achieved by the concerted action of glutathione peroxidase 4 (GPX4) and endogenous lipophilic antioxidants such as ubiquinone and vitamin E. More recently, ferroptosis suppressor protein 1 (FSP1) was identified as a critical ferroptosis inhibitor, acting via the regeneration of membrane-embedded antioxidants.
By Izadora de Souza, Biplab Ghosh, Florencio Porto Freitas, Zhiyi Chen, Shibo Sun, Palina Nepachalovich, Juliane Tschuck, Apoorva Mathur, Ariane Nunes-Alves, Jannik Buhr, Camilo Aponte-Santamaría, Werner Schmitz, Matthias Mack, Martin Eilers, Ralf Bargou, Milena Chaufan, Mayher Kaur, Mario Palma, Jessalyn M. Ubellacker, Ulrich Elling, Hellmut G. Augustin, Kamyar Hadian, Svenja Meierjohann, Bettina Proneth, Marcus Conrad, Maria Fedorova, Hamed Alborzinia, Vera Skafar, Merce Donate Castillo, Lars Seufert, Sebastian Bothe
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Nature
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Bloodbath Nation
Dies ist Paul Austers sehr persönliche Abrechnung mit der Vergottung des Waffentragens in der amerikanischen Kultur und Gesellschaft. Er erzählt davon zunächst in biografischen Vignetten, beginnend bei den Spielzeugcolts der Kindheit und den Western im Fernsehen. Es folgen die ersten Einschläge im näheren Umfeld, der von der Großmutter erschossene Großvater – lange Zeit ein Familiengeheimnis, von dem Auster nur durch Zufall erfuhr.
7-Dehydrocholesterol is an endogenous suppressor of ferroptosis - Nature
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Abstract Ferroptosis is a form of cell death that has received considerable attention not only as a means to eradicate defined tumour entities but also because it provides unforeseen insights into the metabolic adaptation that tumours exploit to counteract phospholipid oxidation1,2. Here, we identify proferroptotic activity of 7-dehydrocholesterol reductase (DHCR7) and an unexpected prosurvival function of its substrate, 7-dehydrocholesterol (7-DHC).
By Florencio Porto Freitas, Palina Nepachalovich, Omkar Zilka, Sebastian Doll, Werner Schmitz, Ann M. Wehman, Isabel Weigand, Matthias Kroiss, Fernando Gomes, Manjima B Sathian, David B. Konrad, Douglas Covey, Ralf Bargou, Ana J. García-Sáez, Derek Pratt, Maria Fedorova, Andreas Trumpp, Marcus Conrad, Alex Inague, Karoly Mirnics
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Nature
Verified
Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1α-mediated glycolytic reprogramming - Nature Communications
Abstract T cell exhaustion is a hallmark of cancer and persistent infections, marked by inhibitory receptor upregulation, diminished cytokine secretion, and impaired cytolytic activity. Terminally exhausted T cells are steadily replenished by a precursor population (Tpex), but the metabolic principles governing Tpex maintenance and the regulatory circuits that control their exhaustion remain incompletely understood.
Baumgartner
Professor Sxdney T.
An engineered variant of MECR reductase reveals indispensability of long-chain acyl-ACPs for mitochondrial respiration - Nature Communications
Abstract Mitochondrial fatty acid synthesis (mtFAS) is essential for respiratory function. MtFAS generates the octanoic acid precursor for lipoic acid synthesis, but the role of longer fatty acid products has remained unclear. The structurally well-characterized component of mtFAS, human 2E-enoyl-ACP reductase (MECR) rescues respiratory growth and lipoylation defects of a Saccharomyces cerevisiae Δetr1 strain lacking native mtFAS enoyl reductase.
Glycolytic flux control by drugging phosphoglycolate phosphatase - Nature Communications
Abstract Targeting the intrinsic metabolism of immune or tumor cells is a therapeutic strategy in autoimmunity, chronic inflammation or cancer. Metabolite repair enzymes may represent an alternative target class for selective metabolic inhibition, but pharmacological tools to test this concept are needed. Here, we demonstrate that phosphoglycolate phosphatase (PGP), a prototypical metabolite repair enzyme in glycolysis, is a pharmacologically actionable target.
LXRα activation and Raf inhibition trigger lethal lipotoxicity in liver cancer - Nature Cancer
Abstract The success of molecular therapies targeting specific metabolic pathways in cancer is often limited by the plasticity and adaptability of metabolic networks. Here we show that pharmacologically induced lipotoxicity represents a promising therapeutic strategy for the treatment of hepatocellular carcinoma (HCC). LXRα-induced liponeogenesis and Raf-1 inhibition are synthetic lethal in HCC owing to a toxic accumulation of saturated fatty acids.
Mevalonate Pathway Provides Ubiquinone to Maintain Pyrimidine Synthesis and Survival in p53-Deficient Cancer Cells Exposed to Metabolic Stress
Metabolism and Chemical Biology Irem Kaymak, Carina R. Maier, Werner Schmitz, Andrew D. Campbell, Beatrice Dankworth, Carsten P. Ade, Susanne Walz, Madelon Paauwe, Charis Kalogirou, Hecham Marouf, Mathias T. Rosenfeldt, David M. Gay, Grace H. McGregor, Owen J. Sansom and Almut Schulze DOI: 10.1158/0008-5472.CAN-19-0650 Published January 2020 Abstract Oncogene activation and loss of tumor suppressor function changes the metabolic activity of cancer cells to drive unrestricted proliferation.
Mevalonate Pathway Provides Ubiquinone to Maintain Pyrimidine Synthesis and Survival in p53-Deficient Cancer Cells Exposed to Metabolic Stress
Metabolism and Chemical Biology Irem Kaymak, Carina R. Maier, Werner Schmitz, Andrew D. Campbell, Beatrice Dankworth, Carsten P. Ade, Susanne Walz, Madelon Paauwe, Charis Kalogirou, Hecham Marouf, Mathias T. Rosenfeldt, David M. Gay, Grace H. McGregor, Owen J. Sansom and Almut Schulze DOI: 10.1158/0008-5472.CAN-19-0650 Abstract Oncogene activation and loss of tumor suppressor function changes the metabolic activity of cancer cells to drive unrestricted proliferation.
Mevalonate pathway provides ubiquinone to maintain pyrimidine synthesis and survival in p53-deficient cancer cells exposed to metabolic stress
Research Article Irem Kaymak, Carina Ramona Maier, Werner Schmitz, Andrew D Campbell, Beatrice Dankworth, Carsten P Ade, Susanne Walz, Madelon Paauwe, Charis Kalogirou, Hecham Marouf, Mathias T. Rosenfeldt, David M Gay, Grace H McGregor, Owen J. Sansom and Almut Schulze DOI: 10.1158/0008-5472.CAN-19-0650 Abstract Oncogene activation and loss of tumor suppressor function changes the metabolic activity of cancer cells to drive unrestricted proliferation.
A MYC-GCN2-eIF2α negative feedback loop limits protein synthesis to prevent MYC-dependent apoptosis in colorectal cancer
Abstract Tumours depend on altered rates of protein synthesis for growth and survival, which suggests that mechanisms controlling mRNA translation may be exploitable for therapy. Here, we show that loss of APC, which occurs almost universally in colorectal tumours, strongly enhances the dependence on the translation initiation factor eIF2B5. Depletion of eIF2B5 induces an integrated stress response and enhances translation of MYC via an internal ribosomal entry site.
The kinase PKD3 provides negative feedback on cholesterol and triglyceride synthesis by suppressing insulin signaling
A limit for liver lipid overload Hepatocytes respond to insulin by accumulating triglycerides and cholesterol. Excessive lipid accumulation in the liver can result in nonalcoholic fatty liver disease (NAFLD), the more severe forms of which are risk factors for the development of liver cirrhosis and cancer. Mayer et al. found that activation of PKD3 by insulin signaling served as a negative feedback mechanism to prevent hepatic lipid accumulation.
Die Akte Skripal: Der neue Spionagekrieg und Russlands langer Arm in den Westen: Amazon.de: Mark Urban, Pieke Biermann, Elisabeth Liebl, Werner Schmitz, Karl Heinz Siber, Karsten Singelmann, Henriette Zeltner: Bücher
Es ist ein True-Life Le Carré: Im Frühjahr 2018 werden der ehemalige russische Doppelagent Sergej Skripal und seine Tochter Julija in England mit lebensbedrohlichen Vergiftungserscheinungen aufgefunden. Es gibt kaum Zweifel daran, dass der russische Geheimdienst hinter dem Anschlag mit dem Nervengift Nowitschok steckt.
Größer als das Amt: Auf der Suche nach der Wahrheit
James B. Comey, geb. 1960, hat Jura in Chicago studiert und arbeitete danach bei der New Yorker Staatsanwaltschaft und als Generalstaatsanwalt in Virginia, bis er 2003 zum stellvertretenden Justizminister aufstieg. Danach ging er in die Wirtschaft, bis Präsident Obama den auch an der Columbia Law School Lehrenden 2013 zum FBI Direktor ernannte.
Feuer und Zorn: Im Weißen Haus von Donald Trump eBook: Michael Wolff, Dirk van Gunsteren, Werner Schmitz, Nikolaus Stingl, Gregor Hens, Jan Schönherr, Thomas Gunkel, Isabel Bogdan: Amazon.de: Kindle-Shop
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