--- _id: '1346' abstract: - lang: eng 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. 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." article_number: '11710' article_processing_charge: No author: - first_name: Wim full_name: Dejonghe, Wim last_name: Dejonghe - first_name: Sabine full_name: Kuenen, Sabine last_name: Kuenen - first_name: Evelien full_name: Mylle, Evelien last_name: Mylle - first_name: Mina K full_name: Vasileva, Mina K id: 3407EB18-F248-11E8-B48F-1D18A9856A87 last_name: Vasileva - first_name: Olivier full_name: Keech, Olivier last_name: Keech - first_name: Corrado full_name: Viotti, Corrado last_name: Viotti - first_name: Jef full_name: Swerts, Jef last_name: Swerts - first_name: Matyas full_name: Fendrych, Matyas id: 43905548-F248-11E8-B48F-1D18A9856A87 last_name: Fendrych orcid: 0000-0002-9767-8699 - first_name: Fausto full_name: Ortiz Morea, Fausto last_name: Ortiz Morea - first_name: Kiril full_name: Mishev, Kiril last_name: Mishev - first_name: Simon full_name: Delang, Simon last_name: Delang - first_name: Stefan full_name: Scholl, Stefan last_name: Scholl - first_name: Xavier full_name: Zarza, Xavier last_name: Zarza - first_name: Mareike full_name: Heilmann, Mareike last_name: Heilmann - first_name: Jiorgos full_name: Kourelis, Jiorgos last_name: Kourelis - first_name: Jaroslaw full_name: Kasprowicz, Jaroslaw last_name: Kasprowicz - first_name: Le full_name: Nguyen, Le last_name: Nguyen - first_name: Andrzej full_name: Drozdzecki, Andrzej last_name: Drozdzecki - first_name: Isabelle full_name: Van Houtte, Isabelle last_name: Van Houtte - first_name: Anna full_name: Szatmári, Anna last_name: Szatmári - first_name: Mateusz full_name: Majda, Mateusz last_name: Majda - first_name: Gary full_name: Baisa, Gary last_name: Baisa - first_name: Sebastian full_name: Bednarek, Sebastian last_name: Bednarek - first_name: Stéphanie full_name: Robert, Stéphanie last_name: Robert - first_name: Dominique full_name: Audenaert, Dominique last_name: Audenaert - first_name: Christa full_name: Testerink, Christa last_name: Testerink - first_name: Teun full_name: Munnik, Teun last_name: Munnik - first_name: Daniël full_name: Van Damme, Daniël last_name: Van Damme - first_name: Ingo full_name: Heilmann, Ingo last_name: Heilmann - first_name: Karin full_name: Schumacher, Karin last_name: Schumacher - first_name: Johan full_name: Winne, Johan last_name: Winne - first_name: Jirí full_name: Friml, Jirí id: 4159519E-F248-11E8-B48F-1D18A9856A87 last_name: Friml orcid: 0000-0002-8302-7596 - first_name: Patrik full_name: Verstreken, Patrik last_name: Verstreken - first_name: Eugenia full_name: Russinova, Eugenia last_name: Russinova citation: ama: Dejonghe W, Kuenen S, Mylle E, et al. Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification. Nature Communications. 2016;7. doi:10.1038/ncomms11710 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. Nature Communications. Nature Publishing Group. https://doi.org/10.1038/ncomms11710 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.” Nature Communications. Nature Publishing Group, 2016. https://doi.org/10.1038/ncomms11710. ieee: W. Dejonghe et al., “Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification,” Nature Communications, vol. 7. Nature Publishing Group, 2016. 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. mla: Dejonghe, Wim, et al. “Mitochondrial Uncouplers Inhibit Clathrin-Mediated Endocytosis Largely through Cytoplasmic Acidification.” Nature Communications, vol. 7, 11710, Nature Publishing Group, 2016, doi:10.1038/ncomms11710. 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). date_created: 2018-12-11T11:51:30Z date_published: 2016-06-08T00:00:00Z date_updated: 2026-04-08T13:54:44Z day: '08' ddc: - '570' department: - _id: JiFr doi: 10.1038/ncomms11710 ec_funded: 1 external_id: isi: - '000377899800001' file: - access_level: open_access checksum: e8dc81b3e44db5a7718d7f1501ce1aa7 content_type: application/pdf creator: system date_created: 2018-12-12T10:18:47Z date_updated: 2020-07-14T12:44:45Z file_id: '5369' file_name: IST-2016-653-v1+1_ncomms11710_1_.pdf file_size: 3532505 relation: main_file file_date_updated: 2020-07-14T12:44:45Z fulldoi: https://doi.org/10.1038/ncomms11710 has_accepted_license: '1' intvolume: ' 7' isi: 1 language: - iso: eng month: '06' oa: 1 oa_version: Published Version project: - _id: 25716A02-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '282300' name: Polarity and subcellular dynamics in plants publication: Nature Communications publication_status: published publisher: Nature Publishing Group publist_id: '5906' pubrep_id: '653' quality_controlled: '1' related_material: record: - id: '7172' relation: dissertation_contains status: public scopus_import: '1' status: public title: Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345 volume: 7 year: '2016' ...