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  -