Heat shock protein 60 couples an oxidative stress-responsive p38/MK2 signaling and NF-κB survival machinery in cancer cells
- 주제(키워드) HSP60 , Mitochondria , NF-κB , Oxidative stress , p38 MAPK
- 등재 SCIE, SCOPUS
- OA유형 Green Published, gold
- 발행기관 Elsevier B.V.
- 발행년도 2022
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000190329
- 본문언어 영어
- Published As https://doi.org/10.1016/j.redox.2022.102293
- PubMed https://pubmed.ncbi.nlm.nih.gov/35316673
초록/요약
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
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