期刊
MOLECULAR CELL
卷 32, 期 5, 页码 641-651出版社
CELL PRESS
DOI: 10.1016/j.molcel.2008.11.014
关键词
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资金
- INSERM
- AFM [11456, 13291]
- FRM [DEQ20071210550]
- Italian Association for Cancer Research (AIRC)
- Italian University Ministry
- Emilia-Romagna PRRIITT
- Italian Space Agency (ASI)
- Fondazione Telethon Funding Source: Custom
Among the new players at the endoplasmic reticulum (ER)-mitochondria interface regulating interorganelle calcium signaling, those specifically involved during ER stress are not known at present. We report here that the truncated variant of the sarcoendoplasmic reticulum Ca(2+)-ATPase 1 (S1T) amplifies ER stress through the PERK-eIF2 alpha-ATF4-CHOP pathway. SlT, which is localized in the ER-mitochondria microdomains, determines ER Ca(2+) depletion due to increased Ca(2+) leak, an increased number of ER-mitochondria contact sites, and inhibition of mitochondria movements. This leads to increased Ca(2+) transfer to mitochondria in both resting and stimulated conditions and activation of the mitochondrial apoptotic pathway. Interestingly, SlT knockdown was shown to prevent ER stress, mitochondrial Ca(2+) overload, and subsequent apoptosis. Thus, by bridging ER stress to apoptosis through increased ER-mitochondria Ca(2+) transfer, S1T acts as an essential determinant of cellular fate.
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