G protein coupled receptor kinase 2 interacting protein 1 (GIT1) is a novel regulator of mitochondrial biogenesis in heart.
G protein coupled receptor kinase 2 interacting protein 1 (GIT1) is a novel regulator of mitochondrial biogenesis in heart.
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DOI：
10.1016/j.yjmcc.2011.06.020
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发表时间：
2011-11
影响因子：
5
通讯作者：
Berk BC
中科院分区：
文献类型：
--
作者：
Pang J;Xu X;Getman MR;Shi X;Belmonte SL;Michaloski H;Mohan A;Blaxall BC;Berk BC
G蛋白偶联受体（GPCR）-激酶相互作用蛋白1（GIT 1）是一种多功能支架蛋白。然而，人们对其在心脏中的生理作用知之甚少。在这里，我们试图确定GIT 1的心脏功能。产生了GIT 1基因敲除（KO）小鼠，并表现出显著的心脏肥大，进展为心力衰竭。电镜观察显示GIT 1基因敲除小鼠心脏线粒体形态异常，包括线粒体体积密度降低、嵴密度降低和空泡增多。此外，GIT 1 KO小鼠心脏线粒体生物发生相关基因过氧化物酶体增殖物激活受体γ（PPARγ）共激活因子1α（PGC-1α）、PGC-1β、线粒体转录因子A（Tfam）表达和总线粒体DNA均显著降低。这些动物还具有受损的线粒体功能，如通过在成年心肌细胞中ATP产生减少和线粒体膜电位（Atrium）消散所证明的。与这些线粒体观察结果一致，GIT 1 KO小鼠表现出心肌细胞凋亡和心功能障碍增强。总之，我们的研究结果确定GIT 1作为线粒体生物发生和功能的新调节因子，这是出生后心脏成熟所必需的。
G-protein-coupled receptor (GPCR)-kinase interacting protein-1 (GIT1) is a multi-function scaffold protein. However, little is known about its physiological role in the heart. Here we sought to identify the cardiac function of GIT1. Global GIT1 knockout (KO) mice were generated and exhibited significant cardiac hypertrophy that progressed to heart failure. Electron microscopy revealed that the hearts of GIT1 KO mice demonstrated significant morphological abnormities in mitochondria, including decreased mitochondrial volume density, cristae density and increased vacuoles. Moreover, mitochondrial biogenesis-related gene peroxisome proliferator-activated receptor γ (PPARγ) co-activator-1α (PGC-1α), PGC-1β, mitochondrial transcription factor A (Tfam) expression, and total mitochondrial DNA were remarkably decreased in hearts of GIT1 KO mice. These animals also had impaired mitochondrial function, as evidenced by reduced ATP production and dissipated mitochondrial membrane potential (Ψm) in adult cardiomyocytes. Concordant with these mitochondrial observations, GIT1 KO mice showed enhanced cardiomyocyte apoptosis and cardiac dysfunction. In conclusion, our findings identify GIT1 as a new regulator of mitochondrial biogenesis and function, which is necessary for postnatal cardiac maturation.
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影响因子：
20.1
作者：
Casey LM;Pistner AR;Belmonte SL;Migdalovich D;Stolpnik O;Nwakanma FE;Vorobiof G;Dunaevsky O;Matavel A;Lopes CM;Smrcka AV;Blaxall BC
通讯作者：
Blaxall BC
影响因子：
64.5
作者：
Puigserver, P;Wu, ZD;Spiegelman, BM
通讯作者：
Spiegelman, BM
影响因子：
15.9
作者：
Finck, BN;Lehman, JJ;Kelly, DP
通讯作者：
Kelly, DP
影响因子：
2.4
作者：
Hislop, AA
通讯作者：
Hislop, AA
影响因子：
3.3
作者：
Brown, MC;Cary, LA;Turner, CE
通讯作者：
Turner, CE