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The type III intermediate filament vimentin regulates organelle distribution and modulates autophagy

Biskou, Olga; Casanova, Victor; Hooper, Kirsty; Kemp, Sadie; Wright, Graham P; Satsangi, Jack; Barlow, Peter; Stevens, Craig

Authors

Olga Biskou

Victor Casanova

Kirsty Hooper

Sadie Kemp

Jack Satsangi



Abstract

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.

Citation

Biskou, O., Casanova, V., Hooper, K., Kemp, S., Wright, G. P., Satsangi, J., …Stevens, C. (2019). The type III intermediate filament vimentin regulates organelle distribution and modulates autophagy. PLOS ONE, 14(1), Article e0209665. https://doi.org/10.1371/journal.pone.0209665

Journal Article Type Article
Acceptance Date Dec 10, 2018
Online Publication Date Jan 30, 2019
Publication Date Jan 30, 2019
Deposit Date Jan 10, 2019
Publicly Available Date Mar 29, 2024
Journal PLOS One
Print ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 14
Issue 1
Article Number e0209665
DOI https://doi.org/10.1371/journal.pone.0209665
Keywords Vimentin; autophagy; lysosomes; autophagosomes; mTORC1;
Public URL http://researchrepository.napier.ac.uk/Output/1496641

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
© 2019 Biskou et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited







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