TY - JOUR
T1 - GRK2 moderates the acute mitochondrial damage to ionizing radiation exposure by promoting mitochondrial fission/fusion
AU - Franco, Antonietta
AU - Sorriento, Daniela
AU - Gambardella, Jessica
AU - Pacelli, Roberto
AU - Prevete, Nella
AU - Procaccini, Claudio
AU - Matarese, Giuseppe
AU - Trimarco, Bruno
AU - Iaccarino, Guido
AU - Ciccarelli, Michele
N1 - Funding Information:
G. I. is supported by a grant from Project of National Relevance (PRIN-2016, GI) funded by Italian Ministry of Research and Instruction (MIUR). M. C. is supported by Young Investigator grant (Ricerca Finalizzata-Giovani Ricercatori, M. C.) from Italian Ministry of Health and funds for basic research (FARB 2015-2016) from University of Salerno. G. M. is supported by a grant from the European Union IDEAS Programme, European Research Council Starting Grant “menTORingTregs” n. 310496 1Department of Advanced Biomedical Sciences, “Federico II” University, Naples, Italy. 2Center for Pharmacogenomics, Washington University in St. Louis, St Louis, USA. 3Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy. 4Department of Translational Medical Sciences, “Federico II” University, Naples, Italy. 5Department of Molecular Medicine and Medical Biotechnologies “Federico II” University, Naples and Institute of Experimental Endocrinology and Oncology (IEOS-CNR), Naples, Italy
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85048040755&partnerID=8YFLogxK
U2 - 10.1038/s41420-018-0028-7
DO - 10.1038/s41420-018-0028-7
M3 - Article
C2 - 29531822
AN - SCOPUS:85048040755
VL - 4
JO - Cell Death Discovery
JF - Cell Death Discovery
SN - 2058-7716
IS - 1
M1 - 25
ER -