Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification
- Author
- Wim Dejonghe (UGent) , Sabine Kuenen, Evelien Mylle (UGent) , Mina Vasileva, Olivier Keech, Corrado Viotti, Jef Swerts, Matyas Fendrych (UGent) , Fausto Andres Ortiz Morea (UGent) , Kiril Mishev (UGent) , Simon Delang, Stefan Scholl, Xavier Zarza, Mareike Heilmann, Jiorgos Kourelis, Jaroslaw Kasprowicz, Long Nguyen (UGent) , Andrzej Drozdzecki (UGent) , Isabelle Vanhoutte (UGent) , Anna Maria Szatmari (UGent) , Mateusz Majda, Gary Baisa, Sebastian York Bednarek, Stephanie Robert (UGent) , Dominique Audenaert (UGent) , Christa Testerink, Teun Munnik, Daniël Van Damme (UGent) , Ingo Heilmann, Karin Schumacher, Johan Winne (UGent) , Jiri Friml (UGent) , Patrik Verstreken and Eugenia Russinova (UGent)
- Organization
- Abstract
- 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.
- Keywords
- ADAPTER COMPLEX, ARABIDOPSIS-THALIANA, OXIDATIVE-PHOSPHORYLATION, ALPHA-ADAPTIN, COATED PITS, ANTIMYCIN-A, 5-BISPHOSPHATE, PHOSPHATIDYLINOSITOL 4, PLASMA-MEMBRANE, ATPASE ACTIVITY, TERMINAL DOMAIN
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Dejonghe et al. 2016 Nature Communications 7 11710.pdf
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Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8036372
- MLA
- Dejonghe, Wim, et al. “Mitochondrial Uncouplers Inhibit Clathrin-Mediated Endocytosis Largely through Cytoplasmic Acidification.” NATURE COMMUNICATIONS, vol. 7, 2016, doi:10.1038/ncomms11710.
- APA
- Dejonghe, W., Kuenen, S., Mylle, E., Vasileva, M., Keech, O., Viotti, C., … Russinova, E. (2016). Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification. NATURE COMMUNICATIONS, 7. https://doi.org/10.1038/ncomms11710
- Chicago author-date
- Dejonghe, Wim, Sabine Kuenen, Evelien Mylle, Mina Vasileva, Olivier Keech, Corrado Viotti, Jef Swerts, et al. 2016. “Mitochondrial Uncouplers Inhibit Clathrin-Mediated Endocytosis Largely through Cytoplasmic Acidification.” NATURE COMMUNICATIONS 7. https://doi.org/10.1038/ncomms11710.
- Chicago author-date (all authors)
- Dejonghe, Wim, Sabine Kuenen, Evelien Mylle, Mina Vasileva, Olivier Keech, Corrado Viotti, Jef Swerts, Matyas Fendrych, Fausto Andres Ortiz Morea, Kiril Mishev, Simon Delang, Stefan Scholl, Xavier Zarza, Mareike Heilmann, Jiorgos Kourelis, Jaroslaw Kasprowicz, Long Nguyen, Andrzej Drozdzecki, Isabelle Vanhoutte, Anna Maria Szatmari, Mateusz Majda, Gary Baisa, Sebastian York Bednarek, Stephanie Robert, Dominique Audenaert, Christa Testerink, Teun Munnik, Daniël Van Damme, Ingo Heilmann, Karin Schumacher, Johan Winne, Jiri Friml, Patrik Verstreken, and Eugenia Russinova. 2016. “Mitochondrial Uncouplers Inhibit Clathrin-Mediated Endocytosis Largely through Cytoplasmic Acidification.” NATURE COMMUNICATIONS 7. doi:10.1038/ncomms11710.
- Vancouver
- 1.Dejonghe W, Kuenen S, Mylle E, Vasileva M, Keech O, Viotti C, et al. Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification. NATURE COMMUNICATIONS. 2016;7.
- IEEE
- [1]W. Dejonghe et al., “Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification,” NATURE COMMUNICATIONS, vol. 7, 2016.
@article{8036372, abstract = {{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.}}, articleno = {{11710}}, author = {{Dejonghe, Wim and Kuenen, Sabine and Mylle, Evelien and Vasileva, Mina and Keech, Olivier and Viotti, Corrado and Swerts, Jef and Fendrych, Matyas and Ortiz Morea, Fausto Andres and Mishev, Kiril and Delang, Simon and Scholl, Stefan and Zarza, Xavier and Heilmann, Mareike and Kourelis, Jiorgos and Kasprowicz, Jaroslaw and Nguyen, Long and Drozdzecki, Andrzej and Vanhoutte, Isabelle and Szatmari, Anna Maria and Majda, Mateusz and Baisa, Gary and Bednarek, Sebastian York and Robert, Stephanie and Audenaert, Dominique and Testerink, Christa and Munnik, Teun and Van Damme, Daniël and Heilmann, Ingo and Schumacher, Karin and Winne, Johan and Friml, Jiri and Verstreken, Patrik and Russinova, Eugenia}}, issn = {{2041-1723}}, journal = {{NATURE COMMUNICATIONS}}, keywords = {{ADAPTER COMPLEX,ARABIDOPSIS-THALIANA,OXIDATIVE-PHOSPHORYLATION,ALPHA-ADAPTIN,COATED PITS,ANTIMYCIN-A,5-BISPHOSPHATE,PHOSPHATIDYLINOSITOL 4,PLASMA-MEMBRANE,ATPASE ACTIVITY,TERMINAL DOMAIN}}, language = {{eng}}, pages = {{12}}, title = {{Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification}}, url = {{http://doi.org/10.1038/ncomms11710}}, volume = {{7}}, year = {{2016}}, }
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