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Cold stress‐induced ferroptosis involves the ASK 1‐p38 pathway
Author(s) -
Hattori Kazuki,
Ishikawa Hiroyuki,
Sakauchi Chihiro,
Takayanagi Saki,
Naguro Isao,
Ichijo Hidenori
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201744228
Subject(s) - microbiology and biotechnology , ask price , biology , chemistry , business , finance
A wide variety of cell death mechanisms, such as ferroptosis, have been proposed in mammalian cells, and the classification of cell death attracts global attention because each type of cell death has the potential to play causative roles in specific diseases. However, the precise molecular mechanisms leading to cell death are poorly understood, particularly in ferroptosis. Here, we show that continuous severe cold stress induces ferroptosis and the ASK 1‐p38 MAPK pathway in multiple cell lines. The activation of the ASK 1‐p38 pathway is mediated by critical determinants of ferroptosis: MEK activity, iron ions, and lipid peroxide. The chemical compound erastin, a potent ferroptosis inducer, also activates the ASK 1‐p38 axis downstream of lipid peroxide accumulation and leads to ASK 1‐dependent cell death in a cell type‐specific manner. These lines of evidence provide mechanistic insight into ferroptosis, a type of regulated necrosis.