TY - JOUR
T1 - S-glutathionylation activates STIM1 and alters mitochondrial homeostasis
AU - Hawkins, Brian J.
AU - Irrinki, Krishna M.
AU - Mallilankaraman, Karthik
AU - Lien, Yu Chin
AU - Wang, Youjun
AU - Bhanumathy, Cunnigaiper D.
AU - Subbiah, Ramasamy
AU - Ritchie, Michael F.
AU - Soboloff, Jonathan
AU - Baba, Yoshihiro
AU - Kurosaki, Tomohiro
AU - Joseph, Suresh K.
AU - Gill, Donald L.
AU - Madesh, Muniswamy
PY - 2010/8/9
Y1 - 2010/8/9
N2 - Oxidant stress influences many cellular processes, including cell growth, differentiation, and cell death. A well-recognized link between these processes and oxidant stress is via alterations in Ca2+ signaling. However, precisely how oxidants influence Ca2+ signaling remains unclear. Oxidant stress led to a phenotypic shift in Ca2+ mobilization from an oscillatory to a sustained elevated pattern via calcium release-activated calcium (CRAC)-mediated capacitive Ca2+ entry, and stromal interaction molecule 1 (STIM1)- and Orai1-deficient cells are resistant to oxidant stress. Functionally, oxidant-induced Ca2+ entry alters mitochondrial Ca2+ handling and bioenergetics and triggers cell death. STIM1 is S-glutathionylated at cysteine 56 in response to oxidant stress and evokes constitutive Ca2+ entry independent of intracellular Ca2+ stores. These experiments reveal that cysteine 56 is a sensor for oxidant-dependent activation of STIM1 and demonstrate a molecular link between oxidant stress and Ca2+ signaling via the CRAC channel.
AB - Oxidant stress influences many cellular processes, including cell growth, differentiation, and cell death. A well-recognized link between these processes and oxidant stress is via alterations in Ca2+ signaling. However, precisely how oxidants influence Ca2+ signaling remains unclear. Oxidant stress led to a phenotypic shift in Ca2+ mobilization from an oscillatory to a sustained elevated pattern via calcium release-activated calcium (CRAC)-mediated capacitive Ca2+ entry, and stromal interaction molecule 1 (STIM1)- and Orai1-deficient cells are resistant to oxidant stress. Functionally, oxidant-induced Ca2+ entry alters mitochondrial Ca2+ handling and bioenergetics and triggers cell death. STIM1 is S-glutathionylated at cysteine 56 in response to oxidant stress and evokes constitutive Ca2+ entry independent of intracellular Ca2+ stores. These experiments reveal that cysteine 56 is a sensor for oxidant-dependent activation of STIM1 and demonstrate a molecular link between oxidant stress and Ca2+ signaling via the CRAC channel.
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U2 - 10.1083/jcb.201004152
DO - 10.1083/jcb.201004152
M3 - Article
C2 - 20679432
AN - SCOPUS:77955452960
SN - 0021-9525
VL - 190
SP - 391
EP - 405
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 3
ER -