S-glutathionylation activates STIM1 and alters mitochondrial homeostasis

Brian J. Hawkins, Krishna M. Irrinki, Karthik Mallilankaraman, Yu Chin Lien, Youjun Wang, Cunnigaiper D. Bhanumathy, Ramasamy Subbiah, Michael F. Ritchie, Jonathan Soboloff, Yoshihiro Baba, Tomohiro Kurosaki, Suresh K. Joseph, Donald L. Gill, Madesh Muniswamy

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)391-405
Number of pages15
JournalJournal of Cell Biology
Volume190
Issue number3
DOIs
StatePublished - Aug 9 2010
Externally publishedYes

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Oxidants
Homeostasis
Cysteine
Cell Death
Calcium
Stromal Interaction Molecule 1
Energy Metabolism
Cell Differentiation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Hawkins, B. J., Irrinki, K. M., Mallilankaraman, K., Lien, Y. C., Wang, Y., Bhanumathy, C. D., ... Muniswamy, M. (2010). S-glutathionylation activates STIM1 and alters mitochondrial homeostasis. Journal of Cell Biology, 190(3), 391-405. https://doi.org/10.1083/jcb.201004152

S-glutathionylation activates STIM1 and alters mitochondrial homeostasis. / Hawkins, Brian J.; Irrinki, Krishna M.; Mallilankaraman, Karthik; Lien, Yu Chin; Wang, Youjun; Bhanumathy, Cunnigaiper D.; Subbiah, Ramasamy; Ritchie, Michael F.; Soboloff, Jonathan; Baba, Yoshihiro; Kurosaki, Tomohiro; Joseph, Suresh K.; Gill, Donald L.; Muniswamy, Madesh.

In: Journal of Cell Biology, Vol. 190, No. 3, 09.08.2010, p. 391-405.

Research output: Contribution to journalArticle

Hawkins, BJ, Irrinki, KM, Mallilankaraman, K, Lien, YC, Wang, Y, Bhanumathy, CD, Subbiah, R, Ritchie, MF, Soboloff, J, Baba, Y, Kurosaki, T, Joseph, SK, Gill, DL & Muniswamy, M 2010, 'S-glutathionylation activates STIM1 and alters mitochondrial homeostasis', Journal of Cell Biology, vol. 190, no. 3, pp. 391-405. https://doi.org/10.1083/jcb.201004152
Hawkins BJ, Irrinki KM, Mallilankaraman K, Lien YC, Wang Y, Bhanumathy CD et al. S-glutathionylation activates STIM1 and alters mitochondrial homeostasis. Journal of Cell Biology. 2010 Aug 9;190(3):391-405. https://doi.org/10.1083/jcb.201004152
Hawkins, Brian J. ; Irrinki, Krishna M. ; Mallilankaraman, Karthik ; Lien, Yu Chin ; Wang, Youjun ; Bhanumathy, Cunnigaiper D. ; Subbiah, Ramasamy ; Ritchie, Michael F. ; Soboloff, Jonathan ; Baba, Yoshihiro ; Kurosaki, Tomohiro ; Joseph, Suresh K. ; Gill, Donald L. ; Muniswamy, Madesh. / S-glutathionylation activates STIM1 and alters mitochondrial homeostasis. In: Journal of Cell Biology. 2010 ; Vol. 190, No. 3. pp. 391-405.
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