Mitochondrial localization unveils a novel role for GRK2 in organelle biogenesis.

Authors:
Anna Fusco
Anna Fusco
Federico II University
Gaetano Santulli
Gaetano Santulli
Federico II University of Naples
Italy
Daniela Sorriento
Daniela Sorriento
Department of Clinical Medicine
Italy
Ersilia Cipolletta
Ersilia Cipolletta
Department of Clinical Medicine
Italy
Corrado Garbi
Corrado Garbi
Università di Napoli Federico II
Gerald W Dorn
Gerald W Dorn
Center for Pharmacogenomics
Palo Alto | United States
Bruno Trimarco
Bruno Trimarco
Federico II University
Napoli | Italy
Antonio Feliciello
Antonio Feliciello
Università Federico II
Italy

Cell Signal 2012 Feb 1;24(2):468-75. Epub 2011 Oct 1.

Clinical Medicine, Cardiovascular and Immunological Sciences Federico II University, Naples, Italy.

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.

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Source
http://dx.doi.org/10.1016/j.cellsig.2011.09.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237777PMC

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February 2012
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