Mitochondrial localization unveils a novel role for GRK2 in organelle biogenesis

Cell Signal. 2012 Feb;24(2):468-75. doi: 10.1016/j.cellsig.2011.09.026. Epub 2011 Oct 1.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis*
  • Animals
  • Aorta / cytology
  • Aorta / drug effects
  • Aorta / metabolism*
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • G-Protein-Coupled Receptor Kinase 2 / genetics
  • G-Protein-Coupled Receptor Kinase 2 / metabolism*
  • Humans
  • Hypoxia / metabolism
  • Insulin / metabolism
  • Insulin / pharmacology
  • Insulin Resistance
  • Mice
  • Microscopy, Confocal
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Membranes / ultrastructure
  • Phosphorylation
  • Plasmids
  • Primary Cell Culture
  • Protein Binding
  • RGS Proteins / genetics
  • RGS Proteins / metabolism
  • Reperfusion / adverse effects
  • Signal Transduction* / drug effects
  • Somatomedins / metabolism
  • Somatomedins / pharmacology
  • Transfection

Substances

  • Insulin
  • RGS Proteins
  • Somatomedins
  • Adenosine Triphosphate
  • GRK2 protein, human
  • GRK2 protein, mouse
  • G-Protein-Coupled Receptor Kinase 2