Myocardial-specific GRK2 knockout induces cardiac and mitochondrial dysfunction in response to ionizing radiation exposure

Acute ionizing radiation rapidly impairs cardiac mitochondrial homeostasis and function. Cardiomyocyte-specific deletion of GRK2 markedly worsens early radiation-induced cardiac dysfunction. Loss of GRK2 disrupts mitochondrial quality control, reducing activation of the PINK1/Parkin/DRP1 mitophagy pathway and increasing mitochondrial damage. Following irradiation, GRK2 translocates to mitochondria and supports mitochondrial integrity and stress responses. These findings highlight an unrecognized protective role of mitochondrial GRK2 in the early cardiac response to ionizing radiation exposure.