Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification

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-More, Fausto A and Mishev, Kiril and Delang, Simon and Scholl, Stefan and Zarza, Xavier and Heilmann, Mareike and Kourelis, Jiorgos and Kasprowicz, Jaroslaw and Nguyen, Le Son Long and Drozdzecki, Andrzej and Van Houtte, Isabelle and Szatmári, Anna-Maria and Majda, Mateusz and Baisa, Gary A and Bednarek, Sebastian Y and Robert, Stéphanie and Audenaert, Dominique and Testerink, Christa S and Munnik, Teun and Van Damme, Daniël and Heilmann, Ingo and Schumacher, Karin and Winne, Johan M and Friml, Jiří and Verstreken, Patrik and Russinova, Eugenia (2016) Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification. Nature Communications, 7. Article number: 11710. ISSN 2041-1723

[img] Text
ncomms11710_1_.pdf
Available under License Creative Commons Attribution.
[IST-2016-653-v1+1]
Download (3449Kb)
Official URL: http://dx.doi.org/10.1038/ncomms11710

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.

Item Type: Article
DOI: 10.1038/ncomms11710
Subjects: 500 Science > 570 Life sciences; biology
Research Group: Friml Group
SWORD Depositor: Sword Import User
Depositing User: Sword Import User
Date Deposited: 09 Nov 2016 14:55
Last Modified: 30 Aug 2017 12:00
URI: https://repository.ist.ac.at/id/eprint/653

Actions (login required)

View Item View Item