Mitochondrial localization unveils a novel role for GRK2 in organelle biogenesis

Anna Fusco, Gaetano Santulli, Daniela Sorriento, Ersilia Cipolletta, Corrado Garbi, Gerald W. Dorn, Bruno Trimarco, Antonio Feliciello, Guido Iaccarino

Research output: Contribution to journalArticle

49 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)468-475
Number of pages8
JournalCellular Signalling
Volume24
Issue number2
DOIs
StatePublished - Feb 1 2012

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Keywords

  • ATP production
  • Biogenesis
  • GRK2
  • Ischemia/reperfusion
  • Mitochondria

ASJC Scopus subject areas

  • Cell Biology

Cite this

Fusco, A., Santulli, G., Sorriento, D., Cipolletta, E., Garbi, C., Dorn, G. W., Trimarco, B., Feliciello, A., & Iaccarino, G. (2012). Mitochondrial localization unveils a novel role for GRK2 in organelle biogenesis. Cellular Signalling, 24(2), 468-475. https://doi.org/10.1016/j.cellsig.2011.09.026