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Editorial
. 2018 Mar 16;122(6):796-798.
doi: 10.1161/CIRCRESAHA.118.312787.

RCAN1-Calcineurin Axis and the Set-Point for Myocardial Damage During Ischemia-Reperfusion

J Jose Corbalan  1 , Richard N Kitsis  2
Affiliations
Editorial

RCAN1-Calcineurin Axis and the Set-Point for Myocardial Damage During Ischemia-Reperfusion

J Jose Corbalan et al. Circ Res. .
No abstract available

Keywords: Editorials; RCAN-1; calcineurin; calcium; cell death; ischemia; mitochondrial dynamics.

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Figures

Figure
Figure. RCAN1 modulates tissue damage during myocardial ischemia-reperfusion
Depletion of RCAN1 disinhibits the Ca2+-activated protein phosphatase calcineurin resulting in calcineurin-mediated dephosphorylation of serine 637 in human DRP1. This stimulates the translocation of DRP1 from cytosol to the outer mitochondrial membrane where it promotes mitochondrial fission. Depletion of RCAN1 may also promote mitochondrial fragmentation through decreases in mitochondrial fusion proteins OPA1 and MFN2 (not shown). Fragmented mitochondria manifest decreased Ca2+ uptake, which may reflect their loss of electrical potential difference across the inner mitochondrial membrane (Δψm) or perhaps a more direct action of calcineurin on the mitochondrial Ca2+ import machinery. Impaired uptake of Ca2+ results in elevation of cytosolic Ca2+ concentrations, thereby predisposing to the activation of calpains, Ca2+-activated proteases. Calpains cleave signaling and structural proteins to induce cell death. Activation of calcineurin and calpains in this schema takes place during reperfusion because the activities of these enzymes are inhibited in the acidic environment of ischemia.
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References

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Publication types

Supplementary concepts