Franco Antonietta, Sorriento Daniela, Gambardella Jessica, Pacelli Roberto, Prevete Nella, Procaccini Claudio, Matarese Giuseppe, Trimarco Bruno, Iaccarino Guido, Ciccarelli Michele
1Department of Advanced Biomedical Sciences, "Federico II" University, Naples, Italy.
2Center for Pharmacogenomics, Washington University in St. Louis, St Louis, USA.
Cell Death Discov. 2018 Feb 14;4:25. doi: 10.1038/s41420-018-0028-7. eCollection 2018 Dec.
The modern understanding of the G protein-coupled receptor kinase 2 has grown towards the definition of a stress protein, for its ability to rapidly compartmentalize within the cell in response to acute stimulation. Also, mitochondria can be regulated by GRK2 localization. We show that Ionizing Radiation (IR) exposure acutely damages mitochondria regarding mass, morphology, and respiration, with recovery in a framework of hours. This phenomenon is actively regulated by GRK2, whose overexpression results to be protective, and reciprocally, deletion accelerates degenerative processes. The regulatory effects of the kinase involve a new interactome that includes binding HSP90 and binding and phosphorylation of the key molecules involved in the process of mitochondrial fusion and recovery: MFN-1 and 2.
对G蛋白偶联受体激酶2（GRK2）的现代理解已朝着应激蛋白的定义发展，因为它能够在细胞内对急性刺激做出快速区室化反应。此外，线粒体可受GRK2定位的调控。我们发现，电离辐射（IR）暴露会在质量、形态和呼吸方面对线粒体造成急性损伤，并在数小时内恢复。这一现象受到GRK2的积极调控，其过表达具有保护作用，相反，缺失则会加速退化过程。该激酶的调节作用涉及一个新的相互作用组，其中包括与热休克蛋白90（HSP90）结合以及与参与线粒体融合和恢复过程的关键分子——线粒体融合蛋白1（MFN-1）和线粒体融合蛋白2（MFN-2）结合并使其磷酸化。
