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Editorial
. 2022 Mar 4;130(5):725-727.
doi: 10.1161/CIRCRESAHA.122.320798. Epub 2022 Mar 3.

Luminal Oxidative Regulation of the Ryanodine Receptor: More Sides to the Story?

Chantal J M van Opbergen #  1 , Marta Pérez-Hernández #  1 , Mario Delmar  1
Affiliations
Editorial

Luminal Oxidative Regulation of the Ryanodine Receptor: More Sides to the Story?

Chantal J M van Opbergen et al. Circ Res. .
No abstract available

Keywords: Editorials; calcium; cardiac arrhythmias; reactive oxygen species; ryanodine receptor; sarcoplasmic reticulum.

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Figures

Figure 1;
Figure 1;. Graphic illustration of the positive feedback loop via which mitochondrial dysfunction causes intracellular calcium handling disturbances.
Oxidative stress induces mitochondrial calcium (Ca2+) overload via the MCU. Mitochondrial Ca2+ overload increases reactive oxygen species (ROS) production and oxidizes the ryanodine receptors (RyR2), causing sarcoplasmic reticulum (SR) Ca2+ leakage. Oxidative stress in the SR increases Ero1α expression, causing dissociation of ERp44 from RyR2 and separately stimulating RyR2 Ca2+ leakage. Excessive SR Ca2+ release creates elevated cytosolic Ca2+ levels and free Ca2+ ions will be transported back into the mitochondria via the mitochondrial Ca2+ uniporter (MCU). Disturbed intracellular Ca2+ dynamics will eventually lead to triggered activity and cardiac arrhythmias. Ero1α knockdown or inhibition by EN460 can reduce oxidation levels, restore the RyR2-ERp44 interaction and reduce SR Ca2+ leakage. LTCC, l-type calcium channel; RyR2, ryanodine receptor; SERCA, sarco/endoplasmic reticulum Ca2+-ATPase; PLN, phospholamban; MCU, mitochondrial Ca2+ uniporter; ROS, reactive oxygen species.
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References

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