Premium
Autophagy is induced by hypertonic stress and is associated with microtubule‐dependent pericentrosomsal clustering of autolysosomes
Author(s) -
Nunes Paula,
Ernandez Thomas,
Roth Isabelle,
Qiao Xiaomu,
Feraille Eric,
Brown Dennis,
Hasler Udo
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.728.2
Subject(s) - atg12 , autophagy , nocodazole , microbiology and biotechnology , atg8 , microtubule associated protein , nedd8 , dynein , chemistry , biology , sequestosome 1 , dynactin , autophagosome , proteasome , ubiquitin , microtubule , atg5 , cytoskeleton , cell , biochemistry , ubiquitin ligase , apoptosis , gene
Protein damage is a consequence of hypertonic stress, but whether autophagy contributes to the osmoprotective response is unknown. We show that hypertonicity rapidly induced long‐lived protein degradation, LC3 lipidation and Ptdlns3K‐dependent formation of LC3‐ and ATG12‐positive puncta. Lysosomotropic agents but not nutrient deprivation or rapamycin enhanced LC3 lipidation and ATG12‐positive puncta, indicating that hypertonic stress increases autophagic flux. ATG12 siRNA‐mediated knockdown reduced cell survival by hypertonic stress. We show that hypertonicity induces fast reorganization of microtubule (MT) networks, which is associated with strong MT reorganization at centrosomes. MT remodeling was associated with pericentrosomal clustering of ATG12‐positive autolysosomes that co‐localized with p62 and ubiquitin, indicating that autophagy induced by hypertonic stress is partly selective. Efficient autophagy by hypertonic stress required MT remodeling and was dynein‐dependent as autophagosome clustering was enhanced by paclitaxel‐induced MT stabilization and was reduced by nocodazole‐induced tubulin depolymerization as well as chemical (EHNA) or genetic [dynactin 2 (p50) overexpression] interference of dynein activity. The data document a general and hitherto overlooked mechanism, where autophagy and MT remodeling play prominent roles in the osmoprotective response.