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

Autor: Olga Biskou, Kirsty M Hooper, Graham P. Wright, Craig Stevens, Peter G. Barlow, Sadie Kemp, Victor Casanova, Jack Satsangi
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Autophagosome
Biomedical Science Research Group
Intermediate Filaments
Vimentin
mTORC1
Membrane Fusion
Biochemistry
Microtubules
chemistry.chemical_compound
0302 clinical medicine
Cytosol
Contractile Proteins
QR180 Immunology
Cytoskeleton
Staining
Multidisciplinary
biology
Cell Death
Cell Staining
Immunology and infection
Cell biology
medicine.anatomical_structure
Cell Processes
Health
Medicine
Cellular Structures and Organelles
Signal Transduction
Research Article
autophagy
Autophagic Cell Death
Science
macromolecular substances
Mechanistic Target of Rapamycin Complex 1
Research and Analysis Methods
03 medical and health sciences
lysosomes
616 Diseases
Tubulins
Lysosome
Cell Line
Tumor
medicine
Humans
Mechanistic target of rapamycin
Withanolides
Organelles
Autophagy
Biology and Life Sciences
Proteins
Cell Biology
Actins
Cytoskeletal Proteins
030104 developmental biology
HEK293 Cells
chemistry
Withaferin A
Specimen Preparation and Treatment
biology.protein
autophagosomes
030217 neurology & neurosurgery
Zdroj: PLoS ONE, Vol 14, Iss 1, p e0209665 (2019)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0209665
Popis: 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.
Databáze: OpenAIRE
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