The SR/ER-mitochondria calcium crosstalk is regulated by XXXX during reperfusion injury.

@entity671 @entity9197 @entity519 @entity741 @entity112 @entity141 @entity9459
UNASSIGNED: @entity9459 ( @entity9459 ) is a multifunctional kinase whose inhibition is known to limit @entity741 -reperfusion injury. However, the mechanism mediating this beneficial effect still remains unclear. Mitochondria and sarco/endoplasmic reticulum (SR/ER) are key players in cell death signaling. Their involvement in @entity741 -reperfusion injury has gained recognition recently, but the underlying mechanisms are not yet well understood. We questioned here whether @entity9459 might have a role in the @entity141 transfer from SR/ER to mitochondria at reperfusion. We showed that a fraction of @entity9459 protein is localized to the SR/ER and mitochondria-associated ER membranes (MAMs) in the heart, and that @entity9459 specifically interacted with the @entity671 receptors (IP3Rs) @entity141 channeling complex in MAMs. We demonstrated that both pharmacological and genetic inhibition of @entity9459 decreased protein interaction of @entity9197 with the @entity141 channeling complex, impaired SR/ER @entity141 release and reduced the @entity112 -stimulated @entity141 exchange between SR/ER and mitochondria in cardiomyocytes. During @entity519 reoxygenation, cell death is associated with an increase of @entity9459 activity and @entity9197 phosphorylation, which leads to enhanced transfer of @entity141 from SR/ER to mitochondria. Inhibition of @entity9459 at reperfusion reduced both @entity9197 phosphorylation and SR/ER @entity141 release, which consequently diminished both cytosolic and mitochondrial @entity141 concentrations, as well as sensitivity to apoptosis. We conclude that inhibition of @entity9459 at reperfusion diminishes @entity141 leak from @entity9197 at MAMs in the heart, which limits both cytosolic and mitochondrial @entity141 overload and subsequent cell death.
