title: S-glutathionylation activates STIM1 and alters mitochondrial homeostasis.
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 Ca(2+) signaling. However, precisely how oxidants influence Ca(2+) signaling remains unclear. Oxidant stress led to a phenotypic shift in Ca(2+) mobilization from an oscillatory to a sustained elevated pattern via calcium release-activated calcium (CRAC)-mediated capacitive Ca(2+) entry, and stromal interaction molecule 1 (STIM1)- and Orai1-deficient cells are resistant to oxidant stress. Functionally, oxidant-induced Ca(2+) entry alters mitochondrial Ca(2+) handling and bioenergetics and triggers cell death. STIM1 is S-glutathionylated at cysteine 56 in response to oxidant stress and evokes constitutive Ca(2+) entry independent of intracellular Ca(2+) 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 Ca(2+) signaling via the CRAC channel.
authors.affiliation: Department of Biochemistry, Temple University, Philadelphia, PA 19140, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Hawkins
authors.forename: Krishna M
authors.initials: KM
authors.lastname: Irrinki
authors.forename: Karthik
authors.initials: K
authors.lastname: Mallilankaraman
authors.forename: Yu-Chin
authors.initials: YC
authors.lastname: Lien
authors.forename: Youjun
authors.initials: Y
authors.lastname: Wang
authors.forename: Cunnigaiper D
authors.initials: CD
authors.lastname: Bhanumathy
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Subbiah
authors.forename: Michael F
authors.initials: MF
authors.lastname: Ritchie
authors.forename: Jonathan
authors.initials: J
authors.lastname: Soboloff
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Baba
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Joseph
authors.forename: Donald L
authors.initials: DL
authors.lastname: Gill
authors.forename: Muniswamy
authors.initials: M
authors.lastname: Madesh
mesh_terms: D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002645:Chickens; D002522:Chlorocebus aethiops; D005978:Glutathione / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D005978:Glutathione