Published in

Nature Research, Nature Communications, 1(7), 2016

DOI: 10.1038/ncomms11710

Links

Tools

Export citation

Search in Google Scholar

Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification

Journal article published in 2016 by Wim Dejonghe, Sabine Kuenen, Evelien Mylle, Mina Vasileva, Olivier Keech ORCID, Corrado Viotti, Jef Swerts, Matyas Fendrych, Fausto A. Ortiz-More, Kiril Mishev ORCID, Simon Delang, Stefan Scholl, Xavier Zarza, Mareike Heilmann, Jiorgos Kourelis and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Green circle
Preprint: archiving allowed
Upload
Red circle
Postprint: archiving forbidden
Green circle
Published version: archiving allowed
Upload
Policy details
Data provided by SHERPA/RoMEO

Abstract

AbstractATP 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.