Chinese Journal of Biochemistry and Molecular Biology PGC-1 . PGC-1. PGC-1β PRC PGC-1 3

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1 ISSN CN / Q Chinese Journal of Biochemistry and Molecular Biology ~ 603 PGC-1 * γ 1 PGC-1 PGC-1α PGC-1β PRC PGC-1 3 PGC-1α PGC-1β PRC PGC-1 PGC-1β PGC-1 γ -1 Q756 Q789 Biological Characters and Functions of Peroxisome Proliferator-activated Receptor γ Coactivator- PGC-1 Family JI Hong LU Rong-Hua CHANG Zhi-Guang YANG Gong-She * Laboratory of Animal Fat Deposition and Muscle Development College of Animal Science and Technology Northwest Sci-Tech University of Agriculture and Forestry Yangling Shaanxi China Abstract Peroxisome proliferator-activated receptor PPAR γ coactivator-1 PGC-1 family contains three numbers PGC-1α PGC-1β and PRC PGC-1-related coactivator This family plays an important role during several metabolism processes including adaptive thermogenesis mitochondrial biogenesis lipid metabolism regulating the balance of blood sugar and glucose transport as well as activating key enzyme of gluconeogenesis and influencing the switch of muscle fiber types There are some differences between the numbers in physiological function and the function described above of PGC-1α while PGC- 1β has unique features in the regulation of adipocyte differentiation and lipid metabolism but the function of PRC was found only in the regulation of mitochondrial biosynthesis and cell proliferation Studies suggested that it can be a therapy for some deseases such as obesity and diabetes by regulating the physiological functions of PGC-1 family especially PGC-1β The latter may be a new drug targets for improving insulin resistance in the body So this article gives a brief overview on the characteristics physiological functions and interaction of the PGC-1 family members Key words peroxisome proliferators activated receptor-gamma coactivator 1 PGC-1 adipocyte differentiation mitochondrial development adaptive thermogenesis muscle fiber types No 2006AA10Z138 No * Tel gsyang999@ hotmail com Received November Accepted April Supported by National High Technology Research and Development Program of China 863 Program No 2006AA10Z138 and China Postdoctoral Science Foundation Funded Project No * Corresponding author Tel gsyang999@ hotmail com

2 7 PGC γ 48% Fig 1 PGC-1α A 1 peroxisome proliferators activated receptor-gamma 3 1 coactivator 1 PGC-1 3 PGC-1α PGC-1β PGC-1 PRC PPAR γ NRF MEF2C PRC PGC-1α PGC-1β 6 PGC-1 RNA PGC-1β Fig 1 β 1 PGC-1 PGC-1 Fig 1 Structure and function of the PGC-1 family coactivators available sequence homology of PGC-1α 1 PGC-1 red Arg / Ser-rich domain yellow and RNA binding PGC-1 4p15 1 domain purple are present in all three PGC-1 family 2 3 PGC-1 members PGC-1α and PGC-1β share an additional domain 1 of similarity in the central region PPARγ 2 Donovan 4 PGC-1 PGC-1 PGC-1β PGC-1 PGC-1α PGC-1β LXXLL PGC-1β and PRC 6 Note that activation do-main 7 Fig PGC-1α PGC-1α N 40% 35% 1 C RNA Fig 2 Conservation of the PGC-1 family of coactivators in vertebrates 7 Amino acid sequences of the PGC-1 family of coactivators currently available in the GenBank database are aligned using the Clustal program

3 cdna PGC TPPTTPP DHDYCQ 4 PGC-1 PGC-1α PGC-1α PGC-1α PGC-1β C PGC-1α RNA RS TRAP / DRIP 8 LeMoine 12 mrna 9 PGC-1β PPAR NRF-1 mrna 2 PGC-1 PGC-1α PGC-1β PGC-1α 4 PGC-1α 35 PGC-1β PGC-1α PGC-1β PGC-1β PGC-1α McClelland PGC-1α PGC-1β ATP PGC-1α β UCPs UCP-1 PGC-1α PGC-1α mrna 11 PGC-1β 1 UCP-1 18 PGC-1β BAT PGC-1α UCP-1 19 PGC-1β β 12 PGC-1α PGC-1β 4 PGC-1α PRC UCP-1 20 PGC-1α UCP-1 LeMoine 12 WAT PRC PGC-1α UCP-1 PGC-1β / PRC 3 PGC PGC-1α PGC-1α NRFs PGC- A mtfa 1α PGC-1α NRF-1 ER NRF-2 A PPARγ 13 PGC-1α SREBP 14 FOXO1 15 Sox9 16 PGC PGC-1α PGC-1α PGC-1α 2 UCP-2 NRFs 1α PGC-1α 21 PGC-1α GLUT4

4 7 PGC PGC-1α PGC-1β β Krebs 2002 Donovan 4 PGC-1β cdna PGC-1α Tiraby 10 hpgc-1α PGC-1αPPARγ-RXR PGC-1β UCP-1 c CPT-1 PGC-1β PGC-1β PGC-1α PGC-1α PGC-1α 28 PGC-1β PGC-1α PGC-1α PGC-1β 15% ~ 25% PGC-1β PGC-1α PEPCK PGC-1β PGC-1β Hara ERRα PGC-1β 2003 Kamei I 28 PGC-1β cdna 3T3-L1 PGC-1β PGC-1α PGC-1α PGC-1α camp I 3T3-L1 PGC-1α PGC-1β 29 ERRα I I PPARγ PGC-1α ap2 22 PGC-1α DFAT-D1 C3H10T1 /2 PGC-1α PGC-1β Pgc-1α - / - 23 PGC-1β 4 PGC- PGC-1α 1β 30 PGC-1α PGC-1β 26 SNPs 537 Ⅱ ap2 PPARγ 417 PGC-1α 29 Andersen 31 PGC-1β 3 IVS4-11T > C 32 Thr394 Thr Gly 482Ser Gly 482Ser SNPs Ⅱ PGC-1β PGC-1β 7 394Thr-Gly 482Ser Ⅱ 33 St- Goyenechea 27 Pierre 34 PGC-1β Gly 482Ser C2C PGC-1β PGC-1β PGC-1α 75% PGC-1α

5 Cyt c ATP UCP-2 UCP PGC-1β PGC-1β PGC-1β Uldry 35 PRDM16 PGC-1β PRDM16 PGC-1α PGC-1β Vianna 36 PGC-1β % 10% PGC- 1β PGC- PGC- 1β 1 PGC-1α / PGC-1β PGC-1β CtBP PRDM PGC-1β PGC-1β PGC-1β 44 PGC-1β PGC-1β PGC-1β mrna PGC-1β PGC-1β VLDL 40 RNAi PGC-β 3 3 PRC PRC PGC-1α / β C RNA RS A PRC PGC-1 PRC PRC SREBP-1c PGC-1β SREBPs X LXR 14 PGC-1β PGC-1β Foxa2 41 PRC PGC-1α PGC-1β 45 BALB / VLDL PGC-1 PRC PGC-1β 6 PRC LXXLL PGC-1 SREBP PGC-1β NRF-1 LXRα 14 PGC-1β PRC NRF-1 PGC-1β PGC-1 47 ~ 49 PRC PGC-1α PGC-1β RNAi PRC PGC-1β SREBP LXRα VLDL PGC-1β SREBP PGC-1β IL-4 PRC 3T3 PRC mtfa 46 Vercauteren PRC

6 7 PGC PGC-1 PGC-1α PGC-1β PRC 4 PGC-1 PGC-1β cell factor J J Biol Chem PGC-1α PGC-1β PGC-1α J PGC-1β PGC- 1α PGC-1β PGC-1α PGC-1β PGC-1α PGC-1β PGC-1α PGC-1β PGC-1α PGC β UCP-1 90% PGC-1α PGC-1β UCP-1 coactivator PGC-1 J Mol Cell PGC-1α PGC-1β a strategy for the control of fat mass J Metab PRC NRF-1 45 PRC NRF-1 DNA NRF-1 PGC-1 5 PGC-1 J PGC-1 PGC-1 References 1 Finck B N Kelly D P PGC-1 coactivators inducible regulators of energy metabolism in health and disease J J Clin Invest Puigserver P Wu Z Park C W et al A cold inducible coactivator of nuclear receptors linked to adaptive thermogenesis J Cell Esterbauer H Oberkofler H Krempler F et al Human peroxisome proliferator activated receptor gamma coactivator 1 PPARGC1 gene cdna sequence genomic organization chromosomal localization and tissue expression J Genomics Lin J Puigserver P Donovan J et al Peroxisome proliferatorsactivated receptor gamma coactivator 1 beta PGC-1beta a novel PGC-1-related transcription coactivator associated with host Kressler D Schreiber S N Knutti D et al The PGC-1-related protein PERC is a selective coactivator of estrogen receptor alpha J Biol Chem Andersson U Scarpulla R C PGC-1-related coactivator a novel serum-inducible coactivator of nuclear respiratory factor 1- dependent transcription in mammalian cells J Mol Cell Biol 7 Lin J Handschin C Spiegeman B M Metabolic control through the PGC-1 family of transcription coactivators J Cell Metab 8 Wallberg A E Yamamura S Malik S et al Coordination of p300-mediated chromatin remodeling and TRAP / Mediator function through coactivator PGC-1α J Mol Cell Monsalve M Wu Z Adelmant G et al Direct coupling of transcription and mrna processing through the thermogenic 10 Tiraby C Langin D Conversion from white to brown adipocytes Trends Endocrinol 11 PGC-1β cdna J Ji Hong Su Shang-Shun Lu Rong-Hua et al Paritial cdna cloning and preliminary study on expression of PGC-1β in Zebrafish Danio rerio J Acta Agric Boreali-Occidentalis Sin LeMoine C M Genge C E Moyes CD Role of the PGC-1 family in the metabolic adaptation of goldfish to diet and temperature J Exp Biol Puigserver P Spiegelman B M Peroxisome proliferators activated receptor-gamma coactivator 1 alpha PGC-1 alpha transcriptional coactivator and metabolic regulator J Endocr Rev Lin J Yang R Tarr P T et al Hyperlipidemic effects of dietary saturated fats mediated through PGC-1β coactivation of SREBP J Cell Puigserver P Rhee J Donovan J et al Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1 alpha interaction J Nature Kawakami Y Tsuda M Takahashi S et al Transcriptional coactivator PGC-1 alpha regulates chondrogenesis via association with Sox9 J Proc Natl Acad Sci USA

7 McClelland G B Craig P M Dhekney K et al Temperatureand exercise-induced gene expression and metabolic enzyme changes in skeletal muscle of adult zebrafish Danio rerio J J Physiol Nedergaard J Golozoubova V Matthias A et al UCP1 the only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefficiency J Biochim Biophys Acta St-Pierre J Lin J Krauss S et al Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1 alpha and 1 beta PGC-1alpha and PGC-1beta in muscle cells J J Biol Chem Liu J Wu P H Tarr P T et al Defects in adaptive energy metabolism with CNS-L inked hyperactivity in PGC-1α null mice J Cell Wu Z Puigserver P Andersson U et al Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1 J Cell Lin J Wu H Tarr PT et al Transcriptional co-activator PGC-1 alpha drives the formation of slow twitch muscle fibres J Nature Leone T C Lehman J J Finck B N et al PGC-1alpha deficiency causes multi-system energy metabolic derangements muscle dysfunction abnormal weight control and hepatic steatosis J PLoS Biol e Herzig S Long F Jhala US et al CREB regulates hepatic gluconeogenesis through the coactivator PGC-1 J Nature Yoon J C Puigserver P Chen G et al Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1 J Nature Hara K Tobe K Okada T et al A genetic variation in the PGC- 1 gene could confer insulin resistance and susceptibility to type Ⅱdiabetes J Diabetologia Goyenechea E Crujeiras A B Abete I et al Enhanced shortterm improvement of insulin response to a low-caloric diet in obese carriers the Gly482Ser variant of the PGC-1a gene J Diabetes Res Clin Pract Kamei Y Ohizumi H Fujitani Y et al PPAR gamma coactivator1 beta / ERR ligand 1 is an ERR protein ligand whose expression induces a high-energy expenditure and antagonizes obesity J Proc Natl Acad Sci U S A Nobuhiro I Kazuhiro I Kuniko H I et al Estrogen-related receptor alpha modulates the expression of adipogenesis-related genes during adipocyte differentiation J Biochem Biophys Res Commun Cooper M P Uldry M Kajimura S et al Modulation of PGC-1 coactivator pathways in brown fat differentiation through LRP130 J J Biol Chem Andersen G Wegner L Yanagisawa K et al Evidence of an association between genetic variation of the coactivator PGC-1β and obesity J J Med Genet Lu R H Ji H Chang Z G et al Mitochondrial development and the influence of its dysfunction during rat adipocyte differentiation J Mol Biol Rep 2009 Aug 20 Epub ahead of print 33 Finck BN Kelly D P PGC-1 coactivators inducible regulators of energy metabolism in health and disease J J Clin Invest St-Pierre J Lin J Krauss S et al Bioenergetic analysis-1 of peroxisome proliferator-activated receptor gamma coactivators-l alpha and -1 beta PGC-1alpha and PGC-1beta in muscle cells J J Biol Chem Uldry M Yang W L St-Pierre J et al Complementary action of the PGC-1 coactivator in mitochondrial biogenesis and brown fat diffentioation J Cell Metab Vianna C R Huntgeburth M Coppari R et al Hypomorphic mutation of PGC-1β causes mitochondrial dysfunction and liver insulin resistance J Cell Metab Wilson-Fritch L Burkart A Bell G et al Mitochondrial biogenesis and remolding during adipogenesis and in response to the insulin sensitiser rosiglitazone J Mol Cell Biol McKay R M McKay J P Avery L et al C elegans A model for exploring the genetics of fat storage J Dev Cell Vankoningsloo S Piens M Lecocq C et al Mitochondrial dysfunction induces triglyceride accumulation in 3T3-L1 cells role of fatty acid β-oxidation and glucose J J Lipid Res Nagai Y Yonemitsu S Erion D M et al The role of peroxisome proliferator-activated receptor γ coactivator-1β in the pathogenesis of fructose-induced insulin resistance J Cell Metab Wolfrum C Stoffel M Coactivation of Foxa2 through Pgc-1β promotes liver fatty acid oxidation and triglyceride / VLDL secretion J Cell Metab Seale P Kajimura S Yang W et al Transcriptional control of brown fat determination by PRDM16 J Cell Metab Kajimura S Seale P Spiegelman B M et al Regulation of the brown and white fat gene programs through a PRDM16 / CtBP transcriptional complex J Genes Dev Vats D Mukundan L Odegaard J I et al Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation J Cell Metab Andersson U Scarpulla R C PGC-1-related coactivator a novel serum-inducible coactivator of nuclear respiratory factor 1- dependent transcription in mammalian cells J Mol Cell Biol Savagner F Mirebeau D Jacques C et al PGC-1-related coactivator and targets are upregulated in the thyroid oncocytoma J Biochem Biophys Res Commun

8 7 PGC Vercauteren K Pasko RA Gleyzer N et al PGC-1-related coactivator immediate early expression and characterization of a CREB / NRF-1 binding domain associated with cytochrome c promoter occupancy and respiratory growth J Mol Cell Biol Vercauteren K Gleyzer N Scarpulla RC PGC-1-related coactivator complexes with HCF-1 and NRF-2β in mediating NRF-2 GABP -dependent respiratory gene expression J J Biol Chem Vercauteren K Gleyzer N Scarpulla R C Short hairpin RNAmediated silencing of PGC-1-related coactivator PRC results in a severe respiratory chain deficiency associated with the proliferation of aberrant mitochondria J J Biol Chem Lai L Leone T C Zechner C et al Transcriptional coactivators PGC-1alpha and PGC-l beta control overlapping programs required for perinatal maturation of the heart J Genes Dev The Fifth Editorial Board of Chinese Journal of Biochemistry and Molecular Biology Advisor ZHENG Ji Editor-in-Chief JIA Hong-Ti Associate Editors-in-Chief CHANG Zeng-Yi LI Lin SHANG Yong-Feng SUN Zhi-Xian WANG Lin-Fang WANG Zhi-Zhen YANG Fu-Yu ZHA Xi-Liang Members of Editorial Board alphabetically CHANG Zeng-Yi CHEN Qing-Xi GENG Yun-Qi GU Jun HANG Hai-Ying HE Rong-Qiao HUANG Li JIA Hong-Ti JIANG Cheng-Yu JIAO Bing-Hua KE Yang JIN You-Xin LI Bo-Liang LI Gang LI Gen-Xi LI Gui-Yuan LI Lin LI Ning LI Zai-Ping LIANG Ai-Hua LIANG Song-Ping LIN Qi-Shui LIU De-Fu LIU De-Pei LIU Guo-Qin LIU Jin-yuan MIAO Shi-Ying PENG Jing-Pian QIAN Guan-Xiang QIANG Bo-Qin QU Liang-Hu RAO Zi-He SHI Yun-Yu RUAN Kang-Cheng SHANG Yong-Feng SHOU Cheng-Chao SUN Zhi-Xian WANG Jia-Xi WANG Lin-Fang WANG Zhi-Zhen WEI Qun WEN Jin-Kun XU Gen-Jun YANG Xiao-Ming YE Qi-Nong ZHANG Jin ZHANG Yi ZHOU Jun-Mei ZHU Yu-Xian YANG Fu-Yu YAO Li-Bo YUAN Qin-Sheng ZHANG Nai-Heng ZHOU Chun-Yan ZHU Da-Hai Specially Invited Members of Editorial Board Ray WU USA Robert K YU USA YANG Ke-Gong YAO Ren-Jie ZHA Xi-Liang ZHANG Xu-Jia ZHOU Hai-Meng ZHU Wei-Guo