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

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: Jan 10, 2019
• 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