title: Mitochondrial localization unveils a novel role for GRK2 in organelle biogenesis.
abstract: Metabolic stimuli such as insulin and insulin like growth factor cause cellular accumulation of G protein coupled receptor kinase 2 (GRK2), which in turn is able to induce insulin resistance. Here we show that in fibroblasts, GRK2 is able to increase ATP cellular content by enhancing mitochondrial biogenesis; also, it antagonizes ATP loss after hypoxia/reperfusion. Interestingly, GRK2 is able to localize in the mitochondrial outer membrane, possibly through one region within the RGS homology domain and one region within the catalytic domain. In vivo, GRK2 removal from the skeletal muscle results in reduced ATP production and impaired tolerance to ischemia. Our data show a novel sub-cellular localization of GRK2 in the mitochondria and an unexpected role in regulating mitochondrial biogenesis and ATP generation.
authors: Clinical Medicine, Cardiovascular and Immunological Sciences "Federico II" University, Naples, Italy.
authors: Anna
authors: A
authors: Fusco
authors: Clinical Medicine, Cardiovascular and Immunological Sciences "Federico II" University, Naples, Italy.
authors: Gaetano
authors: G
authors: Santulli
authors: Clinical Medicine, Cardiovascular and Immunological Sciences "Federico II" University, Naples, Italy.
authors: Daniela
authors: D
authors: Sorriento
authors: Clinical Medicine, Cardiovascular and Immunological Sciences "Federico II" University, Naples, Italy.
authors: Ersilia
authors: E
authors: Cipolletta
authors: Cellular and Molecular Biology and Pathology "Federico II" University, Naples, Italy.
authors: Corrado
authors: C
authors: Garbi
authors: Internal Medicine, Washington University in St. Louis, MO63110 USA.
authors: Gerald W
authors: GW
authors: Dorn
authors: Clinical Medicine, Cardiovascular and Immunological Sciences "Federico II" University, Naples, Italy.
authors: Bruno
authors: B
authors: Trimarco
authors: Cellular and Molecular Biology and Pathology "Federico II" University, Naples, Italy.
authors: Antonio
authors: A
authors: Feliciello
authors: School of Medicine University of Salerno, Baronissi, (Salerno) 84081, Italy. Electronic address: giaccarino@unisa.it.
authors: Guido
authors: G
authors: Iaccarino
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance; D051379:Mice; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism / Q000648:ultrastructure; D010766:Phosphorylation; D010957:Plasmids; D061251:Primary Cell Culture; D011485:Protein Binding; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism; D015424:Reperfusion / Q000009:adverse effects; D015398:Signal Transduction / Q000187:drug effects; D013002:Somatomedins / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection
chemical_list: D007328:Insulin; D020710:RGS Proteins; D013002:Somatomedins; D000255:Adenosine Triphosphate; C496567:GRK2 protein, human; C496568:GRK2 protein, mouse; D054769:G-Protein-Coupled Receptor Kinase 2