TY - JOUR A1 - Dejonghe, Wim A1 - Kuenen, Sabine A1 - Mylle, Evelien A1 - Vasileva, Mina A1 - Keech, Olivier A1 - Viotti, Corrado A1 - Swerts, Jef A1 - Fendrych, Matyas A1 - Ortiz-Morea, Fausto Andres A1 - Mishev, Kiril A1 - Delang, Simon A1 - Scholl, Stefan A1 - Zarza, Xavier A1 - Heilmann, Mareike A1 - Kourelis, Jiorgos A1 - Kasprowicz, Jaroslaw A1 - Nguyen, Le Son Long A1 - Drozdzecki, Andrzej A1 - Van Houtte, Isabelle A1 - Szatmari, Anna-Maria A1 - Majda, Mateusz A1 - Baisa, Gary A1 - Bednarek, Sebastian York A1 - Robert, Stephanie A1 - Audenaert, Dominique A1 - Testerink, Christa A1 - Munnik, Teun A1 - Van Damme, Daniel A1 - Heilmann, Ingo A1 - Schumacher, Karin A1 - Winne, Johan A1 - Friml, Jiri A1 - Verstreken, Patrik A1 - Russinova, Eugenia T1 - Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification JF - Nature Communications N2 - 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. Y1 - 2016 U6 - https://doi.org/10.1038/ncomms11710 SN - 2041-1723 VL - 7 SP - 1959 EP - 1968 PB - Nature Publ. Group CY - London ER - TY - GEN A1 - Cox, Tom A1 - Maris, Tom A1 - Soetart, Karline A1 - Conley, Daniel A1 - van Damme, Stefan A1 - Meire, Patrick A1 - Middelburg, Jack J. A1 - Vos, Matthijs A1 - Struyf, Eric T1 - A macro-tidal freshwater ecosystem recovering from hypereutrophication : the Schelde lease study N2 - We report a 40 year record of eutrophication and hypoxia on an estuarine ecosystem and its recovery from hypereutrophication. After decades of high inorganic nutrient concentrations and recurring anoxia and hypoxia, we observe a paradoxical increase in chlorophyll-a concentrations with decreasing nutrient inputs. We hypothesise that algal growth was inhibited due to hypereutrophication, either by elevated ammonium concentrations, severe hypoxia or the production of harmful substances in such a reduced environment. We study the dynamics of a simple but realistic mathematical model, incorporating the assumption of algal growth inhibition. It shows a high algal biomass, net oxygen production equilibrium with low ammonia inputs, and a low algal biomass, net oxygen consumption equilibrium with high ammonia inputs. At intermediate ammonia inputs it displays two alternative stable states. Although not intentional, the numerical output of this model corresponds to observations, giving extra support for assumption of algal growth inhibition. Due to potential algal growth inhibition, the recovery of hypereutrophied systems towards a classical eutrophied state, will need reduction of waste loads below certain thresholds and will be accompanied by large fluctuations in oxygen concentrations. We conclude that also flow-through systems, heavily influenced by external forcings which partly mask internal system dynamics, can display multiple stable states. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - paper 144 KW - Estuary SW Netherlands KW - southern North-Sea KW - Past 50 years KW - Westerschelde estuary KW - Marine ecosystems Y1 - 2009 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-45180 ER -