| Autor: |
Anindya Roy Chowdhury, Satish Srinivasan, György Csordás, György Hajnóczky, Narayan G. Avadhani |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
iScience, Vol 23, Iss 8, Pp 101370- (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2020.101370 |
| Popis: |
Summary: This study shows that multiple modes of mitochondrial stress generated by partial mtDNA depletion or cytochrome c oxidase disruption cause ryanodine receptor channel (RyR) dysregulation, which instigates the release of Ca2+ in the cytoplasm of C2C12 myoblasts and HCT116 carcinoma cells. We also observed a reciprocal downregulation of IP3R channel activity and reduced mitochondrial uptake of Ca2+. Ryanodine, an RyR antagonist, abrogated the mitochondrial stress-mediated increase in [Ca2+]c and the entire downstream signaling cascades of mitochondrial retrograde signaling. Interestingly, ryanodine also inhibited mitochondrial stress-induced invasive behavior in mtDNA-depleted C2C12 cells and HCT116 carcinoma cells. In addition, co-immunoprecipitation shows reduced FKBP12 protein binding to RyR channel proteins, suggesting the altered function of the Ca2+ channel. These results document how the endoplasmic reticulum-associated RyR channels, in combination with inhibition of the mitochondrial uniporter system, modulate cellular Ca2+ homeostasis and signaling under mitochondrial stress conditions. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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