The type III intermediate filament vimentin regulates organelle distribution and modulates autophagy.
Autophagosomes
/ metabolism
Autophagy
/ physiology
Cell Line, Tumor
Cytoskeleton
/ physiology
Cytosol
HEK293 Cells
Humans
Intermediate Filaments
/ metabolism
Lysosomes
/ metabolism
Mechanistic Target of Rapamycin Complex 1
/ metabolism
Membrane Fusion
/ physiology
Organelles
/ physiology
Signal Transduction
Vimentin
/ metabolism
Withanolides
/ pharmacology
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
14
06
2018
accepted:
10
12
2018
entrez:
31
1
2019
pubmed:
31
1
2019
medline:
5
11
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30699149
doi: 10.1371/journal.pone.0209665
pii: PONE-D-18-17871
pmc: PMC6353089
doi:
Substances chimiques
Vimentin
0
Withanolides
0
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
withaferin A
L6DO3QW4K5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0209665Subventions
Organisme : Chief Scientist Office
ID : ETM/137
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : ETM/389
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : ETM/395
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0800759
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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