Trafficking GRK2: Cellular and Metabolic consequences of GRK2 subcellular localization.

G protein coupled receptor kinase 2 (GRK2) has a key role in cellular function by regulating different intracellular mechanisms in a kinase dependent or independent manner. In this review we have dealt with the recently discovered roles of GRK2 in the regulation of cell metabolism. In particular, we have focused on recent findings about the mitochondrial role of GRK2 in the regulation of energy metabolism. Few findings exist about this topic that all concur to identify a mitochondrial localization of GRK2, leading to the rising of the following question: is GRK2 detrimental or advantageous for mitochondrial function? By the review of available literature, a new concept arises about GRK2 role into the cell,which is that of a stress protein acutely activated by cellular stress whose specific subcellular localization, in particular mitochondrial localization, results in compensatory metabolic responses. Thus, the possibility to regulate GRK2 trafficking within the cell is a promising strategy to regulate the adaptative effects of the kinase on cell metabolism.