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Article Dans Une Revue Cells Année : 2020

Acute Induction of Translocon-Mediated Ca2+ Leak Protects Cardiomyocytes Against Ischemia/Reperfusion Injury

Résumé

During myocardial infarction, dysregulation of Ca 2+ homeostasis between the reticulum, mitochondria, and cytosol occurs in cardiomyocytes and leads to cell death. Ca 2+ leak channels are thought to be key regulators of the reticular Ca 2+ homeostasis and cell survival. The present study aimed to determine whether a particular reticular Ca 2+ leak channel, the translocon, also known as translocation channel, could be a relevant target against ischemia/reperfusion-mediated heart injury. To achieve this objective, we first used an intramyocardial adenoviral strategy to express biosensors in order to assess Ca 2+ variations in freshly isolated adult mouse cardiomyocytes to show that translocon is a functional reticular Ca 2+ leak channel. Interestingly, translocon activation by puromycin mobilized a ryanodine receptor (RyR)-independent reticular Ca 2+ pool and did not affect the excitation-concentration coupling. Second, puromycin pretreatment decreased mitochondrial Ca 2+ content and slowed down the mitochondrial permeability transition pore (mPTP) opening and the rate of cytosolic Ca 2+ increase during hypoxia. Finally, this translocon pre-activation also protected cardiomyocytes after in vitro hypoxia reoxygenation and reduced infarct size in mice submitted to in vivo ischemia-reperfusion. Altogether, our report emphasizes the role of translocon in cardioprotection and highlights a new paradigm in cardioprotection by functionally uncoupling the RyR-dependent Ca 2+ stores and translocon-dependent Ca 2+ stores.
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Dates et versions

hal-03060379 , version 1 (13-12-2020)

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Ribal Al-Mawla, Mallory Ducrozet, Nolwenn Tessier, Lucille Païta, Bruno Pillot, et al.. Acute Induction of Translocon-Mediated Ca2+ Leak Protects Cardiomyocytes Against Ischemia/Reperfusion Injury. Cells, 2020, 9 (5), pp.1319. ⟨10.3390/cells9051319⟩. ⟨hal-03060379⟩
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