Redox regulation of store-operated Ca2+ entry.
CONCLUSIONS
Store-operated Ca2+ entry (SOCE) is a ubiquitous Ca2+ signaling mechanism triggered by Ca2+ depletion of the endoplasmic reticulum (ER) and by a variety of cellular stresses. Reactive oxygen species (ROS) are often concomitantly produced in response to these stresses, however, the relationship between redox signaling and SOCE is not completely understood. Various cardiovascular, neurological, and immune diseases are associated with alterations in both Ca2+ signaling and ROS production, and thus understanding this relationship has therapeutic implications.


BACKGROUND
Several reactive cysteine modifications in stromal interaction molecule (STIM) and Orai proteins comprising the core SOCE machinery were recently shown to modulate SOCE in a redox-dependent manner. Moreover, STIM1 and Orai1 expression levels may reciprocally regulate and be affected by responses to oxidative stress. ER proteins involved in oxidative protein folding have gained increased recognition as important sources of ROS, and the recent discovery of their accumulation in contact sites between the ER and mitochondria provides a further link between ROS production and intracellular Ca2+ handling.


CONCLUSIONS
Future research should aim to establish the complete set of SOCE controlling molecules, to determine their redox-sensitive residues, and to understand how intracellular Ca2+ stores dynamically respond to different types of stress. Mapping the precise nature and functional consequence of key redox-sensitive components of the pre- and post-translational control of SOCE machinery and of proteins regulating ER calcium content will be pivotal in advancing our understanding of the complex cross-talk between redox and Ca2+ signaling.
Department of Cell Physiology and Metabolism, University of Geneva , Geneva, Switzerland .
Paula
P
Nunes
Nicolas
N
Demaurex
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D007477:Ions / Q000378:metabolism; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism
D015220:Calcium Channels; D007477:Ions; D017382:Reactive Oxygen Species; D002118:Calcium