ReviewRegulation of Calcium Homeostasis by ER Redox: A Close-Up of the ER/Mitochondria Connection

- Physical association of the ER and mitochondria plays a pivotal role in the Ca2 + signaling.
- Key proteins controlling the activity of Ca2 + pumps and channels are enriched at the ER/mitochondria junction.
- The activity of Ca2 +-handling proteins is redox-regulated.
- Redox-based regulation of Ca2 + trafficking in the mitochondria-associated membranes is involved in the ER stress response and pro-apoptotic program launch.
- This review summarizes the current knowledge of redox-based mechanisms that govern Ca2 + signaling at the ER-mitochondria interface.

Calcium signaling plays an important role in cell survival by influencing mitochondria-related processes such as energy production and apoptosis. The endoplasmic reticulum (ER) is the main storage compartment for cell calcium (Ca2 +; ~ 60-500 μM), and the Ca2 + released by the ER has a prompt effect on the homeostasis of the juxtaposed mitochondria. Recent findings have highlighted a close connection between ER redox and Ca2 + signaling that is mediated by Ca2 +-handling proteins. This paper describes the redox-regulated mediators and mechanisms that orchestrate Ca2 + signals from the ER to mitochondria.

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