| Autor: |
Seongchun Min, Ji Yeon Kim, Hyo Min Cho, Sujin Park, Ji Min Hwang, Hyejin You, Young Chan Chae, Won-Jae Lee, Woong Sun, Dongmin Kang, Sanghyuk Lee, Sang Won Kang |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Redox Biology, Vol 51, Iss , Pp 102293- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2213-2317 |
| DOI: |
10.1016/j.redox.2022.102293 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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