Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

The cytoskeletal protein vimentin plays a key role in positioning of organelles within the cytosol and has been linked to the regulation of numerous cellular processes including autophagy, however, how vimentin regulates autophagy remains relatively unexplored. Here we report that inhibition of vimentin using the steroidal lactone Withaferin A (WFA) causes vimentin to aggregate, and this is associated with the relocalisation of organelles including autophagosomes and lysosomes from the cytosol to a juxtanuclear location. Vimentin inhibition causes autophagosomes to accumulate, and we demonstrate this results from modulation of mechanistic target of rapamycin (mTORC1) activity, and disruption of autophagosome-lysosome fusion. We suggest that vimentin plays a physiological role in autophagosome and lysosome positioning, thus identifying vimentin as a key factor in the regulation of mTORC1 and autophagy.

Original publication

DOI

10.1371/journal.pone.0209665

Type

Journal article

Journal

PloS one

Publication Date

30/01/2019

Volume

14

Addresses

School of Applied Sciences, Edinburgh Napier University, Sighthill Campus, Sighthill Court, Edinburgh, United Kingdom.

Keywords

Cell Line, Tumor, Cytoskeleton, Intermediate Filaments, Organelles, Lysosomes, Cytosol, Humans, Vimentin, Signal Transduction, Membrane Fusion, Autophagy, Withanolides, HEK293 Cells, Autophagosomes, Mechanistic Target of Rapamycin Complex 1