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Role of SERCA1 truncated isoform in the proapoptotic calcium transfer from ER to mitochondria during ER stress.


ABSTRACT: 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-eIF2alpha-ATF4-CHOP pathway. S1T, 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, S1T 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.

SUBMITTER: Chami M 

PROVIDER: S-EPMC2676567 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Role of SERCA1 truncated isoform in the proapoptotic calcium transfer from ER to mitochondria during ER stress.

Chami Mounia M   Oulès Bénédicte B   Szabadkai György G   Tacine Rachida R   Rizzuto Rosario R   Paterlini-Bréchot Patrizia P  

Molecular cell 20081201 5


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-eIF2alpha-ATF4-CHOP pathway. S1T, which is localized in the ER-mitochondria microdomains, determines ER Ca(2+) depletion due to increased Ca(2+) leak, an increased number  ...[more]

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