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GRK2 moderates the acute mitochondrial damage to ionizing radiation exposure by promoting mitochondrial fission/fusion.

ABSTRACT: 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.

SUBMITTER: Franco A

PROVIDER: S-EPMC5841414 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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GRK2 moderates the acute mitochondrial damage to ionizing radiation exposure by promoting mitochondrial fission/fusion.

Franco Antonietta A Sorriento Daniela D Gambardella Jessica J Pacelli Roberto R Prevete Nella N Procaccini Claudio C Matarese Giuseppe G Trimarco Bruno B Iaccarino Guido G Ciccarelli Michele M

Cell death discovery 20180214

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 ...[more]

PMID: 29531822

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Project description:Mitochondrial dysfunction is a predominant risk factor in ischemic heart disease, in which the imbalance of mitochondrial fusion and fission deteriorates mitochondrial function and might lead to cardiomyocyte death. C-phycocyanin (C-pc), an active component from blue-green algae, such as Spirulina platensis, has been reported to have anti-apoptosis and anti-oxidation functions. In this study, the effects of C-pc on mitochondrial dynamics of cardiomyocytes was examined using an oxygen-glucose deprivation/reoxygenation (OGD/R) model in H9c2 cells, an in vitro model to study the ischemia in the heart. Cell viability assay showed that C-pc dose-dependently reduced OGD/R-induced cell death. Intracellular reactive oxygen species production induced by OGD/R was decreased in C-pc-treated groups in a dose-dependent manner as well. H9c2 cells subjected to OGD/R showed excessive mitochondrial fission and diminished mitochondrial fusion. C-pc treatment significantly ameliorated unbalanced mitochondrial dynamics induced by OGD/R and regulated mitochondrial remodeling through inhibiting mitochondrial fission while promoting fusion. The enhanced expressions of dynamin 1-like protein and mitochondrial fission 1 protein induced by OGD/R were suppressed by C-pc, while the subdued expressions of mitochondrial fusion proteins mitofusins 1 and 2 and optic atrophy 1 induced by OGD/R increased in C-pc-treated groups. Triple immunofluorescence staining revealed that C-pc treatment reduced the recruitment of dynamin 1-like protein from cytoplasm to mitochondrial membranes. Furthermore, C-pc protected H9c2 cells against OGD/R-induced cytochrome c/apoptotic protease activating factor-1 intrinsic apoptosis and suppressed the phosphorylations of extracellular signal-regulated kinase and c-Jun N-terminal kinase. These results suggest that C-pc protects cardiomyocytes from ischemic damage by affecting mitochondrial fission and fusion dynamics and reducing apoptosis and, thus, may be of potential as a prophylactic or therapeutic agent for ischemic heart disease.

Dataset Information

GRK2 moderates the acute mitochondrial damage to ionizing radiation exposure by promoting mitochondrial fission/fusion.

Publications

GRK2 moderates the acute mitochondrial damage to ionizing radiation exposure by promoting mitochondrial fission/fusion.

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