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// Veronica I. Dumit 1, 2, 3, 4 , Ralf M. Zerbes 5, 6 , Stephanie Kaeser-Pebernard 10 , Michal Rackiewicz 2, 3, 10 , Mona T. Wall 1, 2 , Christine Gretzmeier 2, 3 , Victoria Kuttner 2, 3 , Martin van der Laan 5, 7, 8 , Ralf J. Braun 9 and Jorn Dengjel 1, 2, 3, 7, 10 1 Freiburg Institute for Advanced Studies FRIAS, University of Freiburg, Freiburg, Germany 2 Center for Biological Systems Analysis ZBSA, Freiburg, Germany 3 Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany 4 Core Facility Proteomics, ZBSA, University of Freiburg, Freiburg, Germany 5 Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Freiburg, Germany 6 Faculty of Biology, University of Freiburg, Freiburg, Germany 7 BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany 8 Medical Biochemistry and Molecular Biology, Center for Molecular Signaling, PZMS, Saarland University, Homburg, Germany 9 Institute of Cell Biology, University of Bayreuth, Bayreuth, Germany 10 Department of Biology, University of Fribourg, Fribourg, Switzerland Correspondence to: Jorn Dengjel, email: joern.dengjel@unifr.ch Veronica I. Dumit, email: veronica.dumit@zbsa.uni-freiburg.de Keywords: chemoproteomics, reactive oxygen species, mitochondria, anthraquinone, complex I Received: September 09, 2016 Accepted: March 01, 2017 Published: March 21, 2017 ABSTRACT The anthraquinone emodin has been shown to have antineoplastic properties and a wealth of unconnected effects have been linked to its use, most of which are likely secondary outcomes of the drug treatment. The primary activity of emodin on cells has remained unknown. In the present study we demonstrate dramatic and extensive effects of emodin on the redox state of cells and on mitochondrial homeostasis, irrespectively of the cell type and organism, ranging from the yeast Saccharomyces cerevisiae to human cell lines and primary cells. Emodin binds to redox-active enzymes and its effectiveness depends on the oxidative and respiratory status of cells. We show that cells with efficient respiratory metabolism are less susceptible to emodin, whereas cells under glycolytic metabolism are more vulnerable to the compound. Our findings indicate that emodin acts in a similar way as known uncouplers of the mitochondrial electron transport chain and causes oxidative stress that particularly disturbs cancer cells. |
