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Updated: Jun 10, 2026

Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases
14:57

Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases

Published on: October 10, 2020

S-glutathionylation activates STIM1 and alters mitochondrial homeostasis

Brian J Hawkins1, Krishna M Irrinki, Karthik Mallilankaraman

  • 1Department of Biochemistry, Temple University, Philadelphia, PA 19140, USA.

The Journal of Cell Biology
|August 4, 2010
PubMed

Insights

Oxidant stress alters cell calcium (Ca2+) signaling by shifting it to a sustained elevated pattern through calcium release-activated calcium (CRAC) channels. This molecular link involves STIM1 S-glutathionylation, impacting cell death.

Area of Science:

  • Cellular Biology
  • Oxidative Stress Research
  • Calcium Signaling

Background:

  • Oxidant stress impacts critical cellular functions like growth, differentiation, and death.
  • Alterations in calcium (Ca2+) signaling are linked to oxidant stress, but the precise mechanisms are unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which oxidants influence Ca2+ signaling.
  • To investigate the role of stromal interaction molecule 1 (STIM1) and Orai1 in oxidant-induced Ca2+ changes.

Main Methods:

  • Investigated Ca2+ mobilization patterns under oxidant stress.
  • Utilized STIM1 and Orai1 deficient cell models.
  • Examined STIM1 S-glutathionylation at cysteine 56.
  • Assessed mitochondrial Ca2+ handling and bioenergetics.

Main Results:

  • Oxidant stress induced a shift from oscillatory to sustained Ca2+ entry via calcium release-activated calcium (CRAC) channels.
  • STIM1 and Orai1 deficient cells showed resistance to oxidant stress.
  • STIM1 undergoes S-glutathionylation at cysteine 56, leading to constitutive Ca2+ entry.
  • Oxidant-induced Ca2+ entry affected mitochondrial function and promoted cell death.

Conclusions:

  • Cysteine 56 of STIM1 acts as a sensor for oxidant-dependent activation.
  • A molecular link is established between oxidant stress and Ca2+ signaling through the CRAC channel.
  • Understanding this pathway offers insights into oxidant-induced cell death.

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