Mitochondrial localization unveils a novel role for GRK2 in organelle biogenesis

被引：72

作者：

Fusco, Anna ^{[2
]}

Santulli, Gaetano ^{[2
]}

Sorriento, Daniela ^{[2
]}

Cipolletta, Ersilia ^{[2
]}

Garbi, Corrado ^{[2
]}

Dorn, Gerald W., II ^{[3
]}

Trimarco, Bruno ^{[2
]}

Feliciello, Antonio ^{[2
]}

Iaccarino, Guido ^{[1
]}

机构：

[1] Univ Salerno, Sch Med, I-84081 Baronissi, Salerno, Italy

[2] Univ Naples Federico 2, Naples, Italy

[3] Washington Univ, St Louis, MO 63110 USA

来源：

CELLULAR SIGNALLING | 2012年 / 24卷 / 02期

关键词：

GRK2; Mitochondria; Ischemia/reperfusion; Biogenesis; ATP production; COUPLED RECEPTOR KINASE-2; OXIDATIVE-METABOLISM; INSULIN-RESISTANCE; PROTEIN; ABLATION; CAMP; AKT; SRC;

D O I：

10.1016/j.cellsig.2011.09.026

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：468 / 475

页数：8

共 22 条

[1] Mitochondrial kinases in cell signaling: Facts and perspectives [J].

Antico Arciuch, Valeria G. ;

Alippe, Yael ;

Cecilia Carreras, Maria ;

Jose Poderoso, Juan .

ADVANCED DRUG DELIVERY REVIEWS, 2009, 61 (14) :1234-1249

[2] Control of mitochondria dynamics and oxidative metabolism by cAMP, AKAPs and the proteasome [J].

Carlucci, Annalisa ;

Lignitto, Luca ;

Feliciello, Antonio .

TRENDS IN CELL BIOLOGY, 2008, 18 (12) :604-613

[3] Endothelial α1-adrenoceptors regulate neo-angiogenesis [J].

Ciccarelli, M. ;

Santulli, G. ;

Campanile, A. ;

Galasso, G. ;

Cervero, P. ;

Altobelli, G. G. ;

Cimini, V. ;

Pastore, L. ;

Piscione, F. ;

Trimarco, B. ;

Iaccarino, G. .

BRITISH JOURNAL OF PHARMACOLOGY, 2008, 153 (05) :936-946

[4] Endothelial β2 adrenergic signaling to AKT:: Role of Gi and SRC [J].

Ciccarelli, Michele ;

Cipolletta, Ersilia ;

Santulli, Gaetano ;

Campanile, Alfonso ;

Pumiglia, Kevin ;

Cervero, Pasquale ;

Pastore, Lucio ;

Astone, Dalila ;

Trimarco, Bruno ;

Iaccarino, Guido .

CELLULAR SIGNALLING, 2007, 19 (09) :1949-1955

[5] The G protein coupled receptor kinase 2 plays an essential role in beta-adrenergic receptor-induced insulin resistance [J].

Cipolletta, Ersilia ;

Campanile, Alfonso ;

Santulli, Gaetano ;

Sanzari, Emma ;

Leosco, Dario ;

Campiglia, Pietro ;

Trimarco, Bruno ;

Iaccarino, Guido .

CARDIOVASCULAR RESEARCH, 2009, 84 (03) :407-415

[6]

D Sorriento, HYPERTENSION, V56, P696

[7] Mitofusin 2 tethers endoplasmic reticulum to mitochondria [J].

de Brito, Olga Martins ;

Scorrano, Luca .

NATURE, 2008, 456 (7222) :605-U47

[8] AKT participates in endothelial dysfunction in hypertension [J].

Iaccarino, G ;

Ciccarelli, M ;

Sorriento, D ;

Cipolletta, E ;

Cerullo, V ;

Iovino, GL ;

Paudice, A ;

Elia, A ;

Santulli, G ;

Campanile, A ;

Arcucci, O ;

Pastore, L ;

Salvatore, F ;

Condorelli, G ;

Trimarco, B .

CIRCULATION, 2004, 109 (21) :2587-2593

[9]

INGLESE J, 1993, J BIOL CHEM, V268, P23735

[10] Essential role of beta-adrenergic receptor kinase 1 in cardiac development and function [J].

Jaber, M ;

Koch, WJ ;

Rockman, H ;

Smith, B ;

Bond, RA ;

Sulik, KK ;

Ross, J ;

Lefkowitz, RJ ;

Caron, MG ;

Giros, B .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (23) :12974-12979

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