Open AccessThe type III intermediate filament vimentin regulates organelle distribution and modulates autophagy
Author(s) -
Olga Biskou,
Víctor Casanova,
Kirsty M. Hooper,
Sadie Kemp,
G. Payling Wright,
Jack Satsangi,
Peter G. Barlow,
Craig Stevens
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0209665
Subject(s) - vimentin , microbiology and biotechnology , autophagy , lysosome , organelle , intermediate filament , autophagosome , intermediate filament protein , mtorc1 , biology , cytoskeleton , withaferin a , tfeb , biochemistry , signal transduction , cell , medicine , pi3k/akt/mtor pathway , immunology , apoptosis , immunohistochemistry , pathology , withania somnifera , enzyme , alternative medicine
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.