{"file":[{"access_level":"open_access","checksum":"e8dc81b3e44db5a7718d7f1501ce1aa7","date_created":"2018-12-12T10:18:47Z","content_type":"application/pdf","date_updated":"2020-07-14T12:44:45Z","file_name":"IST-2016-653-v1+1_ncomms11710_1_.pdf","file_id":"5369","creator":"system","relation":"main_file","file_size":3532505}],"day":"08","publisher":"Nature Publishing Group","department":[{"_id":"JiFr"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","file_date_updated":"2020-07-14T12:44:45Z","volume":7,"abstract":[{"text":"ATP production requires the establishment of an electrochemical proton gradient across the inner mitochondrial membrane. Mitochondrial uncouplers dissipate this proton gradient and disrupt numerous cellular processes, including vesicular trafficking, mainly through energy depletion. Here we show that Endosidin9 (ES9), a novel mitochondrial uncoupler, is a potent inhibitor of clathrin-mediated endocytosis (CME) in different systems and that ES9 induces inhibition of CME not because of its effect on cellular ATP, but rather due to its protonophore activity that leads to cytoplasm acidification. We show that the known tyrosine kinase inhibitor tyrphostinA23, which is routinely used to block CME, displays similar properties, thus questioning its use as a specific inhibitor of cargo recognition by the AP-2 adaptor complex via tyrosine motif-based endocytosis signals. Furthermore, we show that cytoplasm acidification dramatically affects the dynamics and recruitment of clathrin and associated adaptors, and leads to reduction of phosphatidylinositol 4,5-biphosphate from the plasma membrane.","lang":"eng"}],"date_created":"2018-12-11T11:51:30Z","publication_status":"published","language":[{"iso":"eng"}],"publication":"Nature Communications","_id":"1346","oa":1,"scopus_import":1,"intvolume":"         7","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"citation":{"short":"W. Dejonghe, S. Kuenen, E. Mylle, M.K. Vasileva, O. Keech, C. Viotti, J. Swerts, M. Fendrych, F. Ortiz Morea, K. Mishev, S. Delang, S. Scholl, X. Zarza, M. Heilmann, J. Kourelis, J. Kasprowicz, L. Nguyen, A. Drozdzecki, I. Van Houtte, A. Szatmári, M. Majda, G. Baisa, S. Bednarek, S. Robert, D. Audenaert, C. Testerink, T. Munnik, D. Van Damme, I. Heilmann, K. Schumacher, J. Winne, J. Friml, P. Verstreken, E. Russinova, Nature Communications 7 (2016).","mla":"Dejonghe, Wim, et al. “Mitochondrial Uncouplers Inhibit Clathrin-Mediated Endocytosis Largely through Cytoplasmic Acidification.” <i>Nature Communications</i>, vol. 7, 11710, Nature Publishing Group, 2016, doi:<a href=\"https://doi.org/10.1038/ncomms11710\">10.1038/ncomms11710</a>.","ama":"Dejonghe W, Kuenen S, Mylle E, et al. Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification. <i>Nature Communications</i>. 2016;7. doi:<a href=\"https://doi.org/10.1038/ncomms11710\">10.1038/ncomms11710</a>","ieee":"W. Dejonghe <i>et al.</i>, “Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification,” <i>Nature Communications</i>, vol. 7. Nature Publishing Group, 2016.","chicago":"Dejonghe, Wim, Sabine Kuenen, Evelien Mylle, Mina K Vasileva, Olivier Keech, Corrado Viotti, Jef Swerts, et al. “Mitochondrial Uncouplers Inhibit Clathrin-Mediated Endocytosis Largely through Cytoplasmic Acidification.” <i>Nature Communications</i>. Nature Publishing Group, 2016. <a href=\"https://doi.org/10.1038/ncomms11710\">https://doi.org/10.1038/ncomms11710</a>.","apa":"Dejonghe, W., Kuenen, S., Mylle, E., Vasileva, M. K., Keech, O., Viotti, C., … Russinova, E. (2016). Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification. <i>Nature Communications</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/ncomms11710\">https://doi.org/10.1038/ncomms11710</a>","ista":"Dejonghe W, Kuenen S, Mylle E, Vasileva MK, Keech O, Viotti C, Swerts J, Fendrych M, Ortiz Morea F, Mishev K, Delang S, Scholl S, Zarza X, Heilmann M, Kourelis J, Kasprowicz J, Nguyen L, Drozdzecki A, Van Houtte I, Szatmári A, Majda M, Baisa G, Bednarek S, Robert S, Audenaert D, Testerink C, Munnik T, Van Damme D, Heilmann I, Schumacher K, Winne J, Friml J, Verstreken P, Russinova E. 2016. Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification. Nature Communications. 7, 11710."},"date_published":"2016-06-08T00:00:00Z","quality_controlled":"1","title":"Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"7172"}]},"project":[{"call_identifier":"FP7","name":"Polarity and subcellular dynamics in plants","_id":"25716A02-B435-11E9-9278-68D0E5697425","grant_number":"282300"}],"month":"06","ec_funded":1,"pubrep_id":"653","year":"2016","oa_version":"Published Version","publist_id":"5906","date_updated":"2023-09-07T12:54:35Z","status":"public","author":[{"last_name":"Dejonghe","first_name":"Wim","full_name":"Dejonghe, Wim"},{"first_name":"Sabine","last_name":"Kuenen","full_name":"Kuenen, Sabine"},{"first_name":"Evelien","last_name":"Mylle","full_name":"Mylle, Evelien"},{"first_name":"Mina K","last_name":"Vasileva","full_name":"Vasileva, Mina K","id":"3407EB18-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Keech","first_name":"Olivier","full_name":"Keech, Olivier"},{"full_name":"Viotti, Corrado","last_name":"Viotti","first_name":"Corrado"},{"last_name":"Swerts","first_name":"Jef","full_name":"Swerts, Jef"},{"last_name":"Fendrych","first_name":"Matyas","orcid":"0000-0002-9767-8699","id":"43905548-F248-11E8-B48F-1D18A9856A87","full_name":"Fendrych, Matyas"},{"full_name":"Ortiz Morea, Fausto","first_name":"Fausto","last_name":"Ortiz Morea"},{"first_name":"Kiril","last_name":"Mishev","full_name":"Mishev, Kiril"},{"full_name":"Delang, Simon","last_name":"Delang","first_name":"Simon"},{"full_name":"Scholl, Stefan","last_name":"Scholl","first_name":"Stefan"},{"full_name":"Zarza, Xavier","first_name":"Xavier","last_name":"Zarza"},{"full_name":"Heilmann, Mareike","first_name":"Mareike","last_name":"Heilmann"},{"first_name":"Jiorgos","last_name":"Kourelis","full_name":"Kourelis, Jiorgos"},{"full_name":"Kasprowicz, Jaroslaw","first_name":"Jaroslaw","last_name":"Kasprowicz"},{"first_name":"Le","last_name":"Nguyen","full_name":"Nguyen, Le"},{"first_name":"Andrzej","last_name":"Drozdzecki","full_name":"Drozdzecki, Andrzej"},{"full_name":"Van Houtte, Isabelle","last_name":"Van Houtte","first_name":"Isabelle"},{"full_name":"Szatmári, Anna","first_name":"Anna","last_name":"Szatmári"},{"last_name":"Majda","first_name":"Mateusz","full_name":"Majda, Mateusz"},{"last_name":"Baisa","first_name":"Gary","full_name":"Baisa, Gary"},{"full_name":"Bednarek, Sebastian","first_name":"Sebastian","last_name":"Bednarek"},{"first_name":"Stéphanie","last_name":"Robert","full_name":"Robert, Stéphanie"},{"full_name":"Audenaert, Dominique","first_name":"Dominique","last_name":"Audenaert"},{"first_name":"Christa","last_name":"Testerink","full_name":"Testerink, Christa"},{"full_name":"Munnik, Teun","last_name":"Munnik","first_name":"Teun"},{"full_name":"Van Damme, Daniël","first_name":"Daniël","last_name":"Van Damme"},{"first_name":"Ingo","last_name":"Heilmann","full_name":"Heilmann, Ingo"},{"first_name":"Karin","last_name":"Schumacher","full_name":"Schumacher, Karin"},{"full_name":"Winne, Johan","first_name":"Johan","last_name":"Winne"},{"orcid":"0000-0002-8302-7596","first_name":"Jirí","last_name":"Friml","full_name":"Friml, Jirí","id":"4159519E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Patrik","last_name":"Verstreken","full_name":"Verstreken, Patrik"},{"last_name":"Russinova","first_name":"Eugenia","full_name":"Russinova, Eugenia"}],"article_number":"11710","ddc":["570"],"acknowledgement":"We thank Yvon Jaillais, Ikuko Hara-Nishimura, Akihiko Nakano, Takashi Ueda and Jinxing Lin for providing materials, Natasha Raikhel, Glenn Hicks, Steffen Vanneste, and Ricardo Tejos for useful suggestions, Patrick Callaerts for providing S2 Drosophila cell cultures, Michael Sixt for providing HeLa cells, Annick Bleys for literature searches, VIB Bio Imaging Core for help with imaging conditions and Martine De Cock for help in preparing the article. This work was supported by the Agency for Innovation by Science\r\nand Technology for a pre-doctoral fellowship to W.D.; the Research fund KU Leuven\r\n(GOA), a Methusalem grant of the Flemish government and VIB to S.K., J.K. and P.V.;\r\nby the Netherlands Organisation for Scientific Research (NWO) for ALW grants\r\n846.11.002 (C.T.) and 867.15.020 (T.M.); the European Research Council (project\r\nERC-2011-StG-20101109 PSDP) (to J.F.); a European Research Council (ERC) Starting\r\nGrant (grant 260678) (to P.V.), the Research Foundation-Flanders (grants G.0747.09,\r\nG094011 and G095511) (to P.V.), the Hercules Foundation, an Interuniversity Attraction\r\nPoles Poles Program, initiated by the Belgian State, Science Policy Office (to P.V.),\r\nthe Swedish VetenskapsRådet grant to O.K., the Ghent University ‘Bijzonder\r\nOnderzoek Fonds’ (BOF) for a predoctoral fellowship to F.A.O.-M., the Research\r\nFoundation-Flanders (FWO) to K.M. and E.R.","type":"journal_article","doi":"10.1038/ncomms11710","has_accepted_license":"1"}