Journal Article

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

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

2019

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Autophagosomes - metabolism / Autophagy / Autophagy (Cytology) / Autophagy - physiology / Biology / Biology and Life Sciences / Caprolactone / Cell death / Cell Line, Tumor / Cytoskeleton / Cytoskeleton - physiology / Cytosol / Disruption / Gastroenterology / HEK293 Cells / Humans / Inhibition / Intermediate filament proteins / Intermediate Filaments - metabolism / Lysosomes / Lysosomes - metabolism / Mechanistic Target of Rapamycin Complex 1 - metabolism / Membrane Fusion - physiology / Metabolism / Organelles / Organelles - physiology / Pathogenesis / Phagocytosis / Phagosomes / Plasmids / Proteins / Rapamycin / Research and Analysis Methods / Signal Transduction / TOR protein / Vimentin / Vimentin - metabolism / Vimentin - physiology / Withanolides - pharmacology