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, Muniswamy Madesh

Producción científica: Articlerevisión exhaustiva

201 Citas (Scopus)

Resumen

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.

Idioma originalEnglish (US)
Páginas (desde-hasta)391-405
Número de páginas15
PublicaciónJournal of Cell Biology
Volumen190
N.º3
DOI
EstadoPublished - ago 9 2010
Publicado de forma externa

ASJC Scopus subject areas

  • Cell Biology

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