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Heat shock protein 60 couples an oxidative stress-responsive p38/MK2 signaling and NF-κB survival machinery in cancer cells

Title
Heat shock protein 60 couples an oxidative stress-responsive p38/MK2 signaling and NF-κB survival machinery in cancer cells
Authors
Min S.Kim J.Y.Cho H.M.Park S.Hwang J.M.You H.Chan Chae Y.Lee W.-J.Sun W.Kang D.Lee S.Kang S.W.
Ewha Authors
강상원
SCOPUS Author ID
강상원scopus
Issue Date
2022
Journal Title
Redox Biology
ISSN
2213-2317JCR Link
Citation
Redox Biology vol. 51
Keywords
HSP60MitochondriaNF-κBOxidative stressp38 MAPK
Publisher
Elsevier B.V.
Indexed
SCIE; SCOPUS scopus
Document Type
Article
Abstract
Mitochondria communicate with other cellular compartments via the secretion of protein factors. Here, we report an unexpected messenger role for heat shock protein 60 (HSP60) as a mitochondrial-releasing protein factor that couples stress-sensing signaling and cell survival machineries. We show that mild oxidative stress predominantly activates the p38/MK2 complex, which phosphorylates mitochondrial fission factor 1 (MFF1) at the S155 site. Such phosphorylated MFF1 leads to the oligomerization of voltage anion-selective channel 1, thereby triggering the formation of a mitochondrial membrane pore through which the matrix protein HSP60 passes. The liberated HSP60 associates with and activates the IκB kinase (IKK) complex in the cytosol, which consequently induces the NF-κB-dependent expression of survival genes in nucleus. Indeed, inhibition of the HSP60 release or HSP60-IKK interaction sensitizes the cancer cells to mild oxidative stress and regresses the tumorigenic growth of cancer cells in the mouse xenograft model. Thus, this study reveals a novel mitonuclear survival axis responding to oxidative stress. © 2022 The Authors
DOI
10.1016/j.redox.2022.102293
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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