PPARGC1A

PPARGC1A
PDBに登録されている構造
PDB	オルソログ検索: RCSB PDBe PDBj
PDBのIDコード一覧
	1XB7, 3B1M, 3CS8, 3D24, 3U9Q, 3V9T, 3V9V, 4QJR, 4QK4
識別子
記号	PPARGC1A, LEM6, PGC-1(alpha), PGC-1v, PGC1, PGC1A, PPARGC1, PGC-1alpha, PPARG coactivator 1 alpha, PGC-1α
外部ID	OMIM: 604517 MGI: 1342774 HomoloGene: 7485 GeneCards: PPARGC1A
遺伝子の位置 (マウス)
染色体	5番染色体 (マウス)
終点	51,725,068 bp
RNA発現パターン
	さらなる参照発現データ
遺伝子オントロジー
分子機能	• promoter-specific chromatin binding; • 転写因子結合; • クロマチン結合; • 血漿タンパク結合; • nuclear receptor binding; • 核酸結合; • DNA結合; • sequence-specific DNA binding; • transcription coactivator activity; • alpha-tubulin binding; • transcription coregulator activity; • androgen receptor binding; • nuclear receptor coactivator activity; • RNA結合; • chromatin DNA binding; • ubiquitin protein ligase binding; • 受容体結合; • estrogen receptor binding; • peroxisome proliferator activated receptor binding;
細胞の構成要素	• 細胞質; • 細胞質基質; • cytosolic ribosome; • 細胞核; • RNAポリメラーゼII; • 尖端樹状突起; • soma; • PML body; • 核質; • intracellular membrane-bounded organelle;
生物学的プロセス	• negative regulation of neuron apoptotic process; • response to dietary excess; • negative regulation of glycolytic process; • response to fructose; • cellular response to interleukin-6; • 周期的プロセス; • cellular response to resveratrol; • response to thyroid hormone; • cellular response to fructose stimulus; • cellular response to ionomycin; • adaptive thermogenesis; • response to ischemia; • 概日リズム; • fatty acid oxidation; • response to metformin; • cellular response to caffeine; • response to electrical stimulus involved in regulation of muscle adaptation; • temperature homeostasis; • cellular response to hypoxia; • cellular response to glucose stimulus; • positive regulation of fatty acid oxidation; • cellular response to transforming growth factor beta stimulus; • positive regulation of progesterone biosynthetic process; • regulation of transcription, DNA-templated; • cellular response to follicle-stimulating hormone stimulus; • アンドロゲン代謝プロセス; • 活性酸素への反応; • positive regulation of mitochondrial DNA metabolic process; • 消化; • response to leucine; • response to norepinephrine; • response to epinephrine; • transcription, DNA-templated; • negative regulation of mitochondrial fission; • positive regulation of transcription, DNA-templated; • positive regulation of glomerular visceral epithelial cell apoptotic process; • response to nutrient levels; • RNAスプライシング; • skeletal muscle atrophy; • 細胞呼吸; • negative regulation of signaling receptor activity; • positive regulation of gluconeogenesis; • transcription initiation from RNA polymerase II promoter; • cellular response to potassium ion; • negative regulation of neuron death; • negative regulation of protein phosphorylation; • positive regulation of cellular respiration; • mRNA processing; • タンパク質の安定化; • mitochondrion organization; • positive regulation of DNA-binding transcription factor activity; • response to electrical stimulus; • circadian regulation of gene expression; • 小脳発生; • positive regulation of ATP biosynthetic process; • regulation of NMDA receptor activity; • galactose metabolic process; • positive regulation of muscle tissue development; • regulation of circadian rhythm; • flavone metabolic process; • 脂肪組織発生; • respiratory electron transport chain; • positive regulation of cellular metabolic process; • response to muscle activity; • cellular response to nitrite; • positive regulation of smooth muscle cell proliferation; • 糖新生; • androgen receptor signaling pathway; • negative regulation of smooth muscle cell proliferation; • 低酸素症への反応; • 有機環状化合物への反応; • cellular glucose homeostasis; • cellular response to tumor necrosis factor; • cellular response to estradiol stimulus; • 老化; • negative regulation of smooth muscle cell migration; • response to activity; • positive regulation of histone acetylation; • cellular response to fatty acid; • マイトファジー; • cellular response to thyroid hormone stimulus; • response to methionine; • 飢餓反応; • response to cold; • cellular response to oxidative stress; • 前脳発生; • cellular response to lipopolysaccharide; • positive regulation of transcription by RNA polymerase II; • positive regulation of mitochondrion organization; • 褐色脂肪細胞の分化; • protein-containing complex assembly; • energy homeostasis; • positive regulation of gene expression; • positive regulation of cold-induced thermogenesis;
	出典:Amigo / QuickGO
オルソログ
	10891
	19017
	ENSG00000109819
	ENSMUSG00000029167
	Q9UBK2
	O70343
	NM_013261; NM_001330751; NM_001330752; NM_001330753
	NM_008904
NP_001317680; NP_001317681; NP_001317682; NP_037393; NP_001341754;
	NP_001341755; NP_001341756; NP_001341757
NP_032930; NP_001389916; NP_001389917; NP_001389918; NP_001389919;
	NP_001389920
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

PPARGC1AまたはPGC-1α（peroxisome proliferator-activated receptor gamma coactivator 1-alpha）は、ヒトではPPARGC1A遺伝子にコードされるタンパク質である^[4]。PPARGC1Aはhuman accelerated regionと呼ばれる、チンパンジーとの共通祖先からの分岐以降に塩基置換率が加速しているゲノム領域（HAR20）と関係しており、そのため類人猿からヒトの分岐に重要な役割を果たした可能性がある^[5]。

PGC-1αは、ミトコンドリア生合成（英語版）のマスターレギュレーター（英語版）である^[6]^[7]^[8]。また、PGC-1αは肝臓における糖新生の主要な調節因子であり、糖新生のための遺伝子発現の増加などを担う^[9]。

機能

PGC-1αはエネルギー代謝に関与する遺伝子を調節する転写コアクチベーターであり、ミトコンドリア生合成のマスターレギュレーターである^[6]^[7]^[8]。このタンパク質は核内受容体のPPARγと相互作用し、それによって複数の転写因子との相互作用が可能となる。また、このタンパク質はCREBや核呼吸因子（nuclear respiratory factor, NRF）とも相互作用し、これらの活性を調節する^[10]。PGC-1αは外部の生理的刺激とミトコンドリア生合成の調節を直接関連付ける役割を果たし^[10]、また筋繊維のタイプの分化を調節する主要な因子でもあり、遅筋繊維の形成を駆動する^[11]。

持久運動はヒトの骨格筋においてPGC-1αの遺伝子を活性化することが示されている^[12]。運動によって骨格筋で誘導されたPGC-1αはオートファジー^[13]と小胞体ストレス応答^[14]を増大させる。

PGC-1αタンパク質は、血圧の制御、細胞のコレステロール恒常性の調節、そして肥満に関与している可能性がある^[10]。

PGC-1αによるSIRT3（英語版）のアップレギュレーションは、ミトコンドリアをより健全にする^[15]。

調節

PGC-1αは外部からのシグナルを統合する主要な因子であると考えられている。PGC-1αは多くの因子によって活性化されることが知られている。

絶食は肝臓のPGC-1αなど、糖新生に関与する遺伝子の発現を増加させる^[16]^[17]。
低温曝露によって強く誘導され、この環境刺激を適応的熱産生（adaptive thermogenesis）へ関連付ける^[18]。
持久運動によって誘導される^[12]。PGC-1αは乳酸代謝を決定する。持久運動時の乳酸の高レベルの蓄積を防ぎ、乳酸をエネルギー源としてより効率的に利用できるようにする^[19]。
SIRT1（英語版）はPGC-1αに結合して脱アセチル化によって活性化し、ミトコンドリア生合成に影響を与えることなく糖新生を誘導する^[20]。

PGC-1αは上流の調節因子の一部に対してポジティブフィードバックを行うことが示されている。

PGC-1αは筋肉のAkt（PKB）とリン酸化Akt（Ser473とThr308）のレベルを上昇させる^[21]。
PGC-1αはカルシニューリンの活性化をもたらす^[22]。

AktとカルシニューリンはどちらもNF-κB（p65）の活性化因子である^[23]^[24]。PGC-1αはこれらを活性化することでNF-κBを活性化しているようである。筋肉ではPGC-1αの誘導後にNF-κB活性の増大がみられることが示されているが^[25]、この発見には議論があり、他のグループはPGC-1がNF-κBの活性を阻害することを示している^[26]。

PGC-1αは急性腎障害時にNADの生合成を駆動し、腎臓の保護に大きな役割を果たすことが示されている^[27]。

臨床的意義

PPARGGC1Aはミトコンドリア代謝に対する保護効果によってパーキンソン病の治療となる可能性が示唆されている^[28]。

さらに、PGC-1αの脳特異的アイソフォームはハンチントン病、筋萎縮性側索硬化症など他の神経変性疾患に役割を果たしている可能性が高いことが同定されている^[29]^[30]。

マッサージ治療はPGC-1αの量を増加させ、新たなミトコンドリアの産生をもたらすようである^[31]^[32]^[33]。

PGC-1αとβ（英語版）は、STAT6（英語版）の上流の活性化に伴うPPARγとの相互作用によって、抗炎症性M2マクロファージの極性化に関与することが示唆されている。PGC-1のSTAT6/PPARγを介したM2マクロファージ活性化効果は独立した研究でも確認されており、さらにPGC-1が炎症性サイトカインの産生を阻害することも示されている^[34]。

PGC-1αは運動中の筋肉から3-アミノイソ酪酸の分泌を担うことが提唱されている^[35]。白色脂肪における3-アミノイソ酪酸の効果には、白色脂肪組織（英語版）の褐色化を促進する熱産生遺伝子の活性化や、その後のバックグラウンド代謝の増加などがある。したがって、3-アミノイソ酪酸はPGC-1αのメッセンジャー分子として作用し、白色脂肪など他の組織でPGC-1α増大の効果がみられることが説明される。

相互作用

PPARGC1Aは次に挙げる因子と相互作用することが示されている。

CREB結合タンパク質（英語版）^[36]
エストロゲン関連受容体α（英語版）（ERRα）^[37]、エストロゲン関連受容体β（英語版）（ERRβ）、エストロゲン関連受容体γ（英語版）（ERRγ）
ファルネソイドX受容体（英語版）^[38]
FBXW7（英語版）^[39]
MED1（英語版）^[40]、MED12（英語版）^[40]、MED14（英語版）^[40]、MED17（英語版）^[40]
NRF1（英語版）^[41]
PPARγ^[36]^[40]
レチノイドX受容体α（英語版）^[42]
甲状腺ホルモン受容体β（英語版）^[43]

出典

^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000029167 - Ensembl, May 2017
^ Human PubMed Reference:
^ Mouse PubMed Reference:
^ Esterbauer H, Oberkofler H, Krempler F, Patsch W (February 2000). "Human peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene: cDNA sequence, genomic organization, chromosomal localization, and tissue expression". Genomics. 62 (1): 98–102. doi:10.1006/geno.1999.5977. PMID 10585775。
^ Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M, Vanderhaeghen P, Haussler D (September 2006). "An RNA gene expressed during cortical development evolved rapidly in humans". Nature. 443 (7108): 167–72. Bibcode:2006Natur.443..167P. doi:10.1038/nature05113. PMID 16915236. S2CID 18107797。
^ ^a ^b Valero T (2014). "Mitochondrial biogenesis: pharmacological approaches". Curr. Pharm. Des. 20 (35): 5507–9. doi:10.2174/138161282035140911142118. hdl:10454/13341. PMID 24606795. Mitochondrial biogenesis is therefore defined as the process via which cells increase their individual mitochondrial mass [3]. ... This work reviews different strategies to enhance mitochondrial bioenergetics in order to ameliorate the neurodegenerative process, with an emphasis on clinical trials reports that indicate their potential. Among them creatine, Coenzyme Q10 and mitochondrial targeted antioxidants/peptides are reported to have the most remarkable effects in clinical trials.
^ ^a ^b Sanchis-Gomar F, García-Giménez JL, Gómez-Cabrera MC, Pallardó FV (2014). "Mitochondrial biogenesis in health and disease. Molecular and therapeutic approaches". Curr. Pharm. Des. 20 (35): 5619–5633. doi:10.2174/1381612820666140306095106. PMID 24606801. Mitochondrial biogenesis (MB) is the essential mechanism by which cells control the number of mitochondria.
^ ^a ^b Dorn GW, Vega RB, Kelly DP (2015). "Mitochondrial biogenesis and dynamics in the developing and diseased heart". Genes Dev. 29 (19): 1981–91. doi:10.1101/gad.269894.115. PMC 4604339. PMID 26443844。
^ Klein MA, Denu JM (2020). "Biological and catalytic functions of sirtuin 6 as targets for small-molecule modulators". Journal of Biological Chemistry. 295 (32): 11021–11041. doi:10.1074/jbc.REV120.011438. PMC 7415977. PMID 32518153。
^ ^a ^b ^c “PPARGC1A PPARG coactivator 1 alpha [Homo sapiens (human) - Gene - NCBI]”. www.ncbi.nlm.nih.gov. 2022年3月5日閲覧。
^ Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O, Michael LF, Puigserver P, Isotani E, Olson EN, Lowell BB, Bassel-Duby R, Spiegelman BM (2002). "Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres". Nature. 418 (6899): 797–801. Bibcode:2002Natur.418..797L. doi:10.1038/nature00904. PMID 12181572. S2CID 4415526。
^ ^a ^b Pilegaard H, Saltin B, Neufer PD (February 2003). "Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle". J. Physiol. 546 (Pt 3): 851–8. doi:10.1113/jphysiol.2002.034850. PMC 2342594. PMID 12563009。
^ Vainshtein A, Tryon LD, Pauly M, Hood DA (2015). "Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle". American Journal of Physiology. 308 (9): C710-719. doi:10.1152/ajpcell.00380.2014. PMC 4420796. PMID 25673772。
^ Wu J, Ruas JL, Estall JL, Rasbach KA, Choi JH, Ye L, Boström P, Tyra HM, Crawford RW, Campbell KP, Rutkowski DT, Kaufman RJ, Spiegelman BM (2011). "The unfolded protein response mediates adaptation to exercise in skeletal muscle through a PGC-1α/ATF6α complex". Cell Metabolism. 13 (2): 160–169. doi:10.1016/j.cmet.2011.01.003. PMC 3057411. PMID 21284983。
^ Ji LL, Yeo D (2019). "Mitochondrial dysregulation and muscle disuse atrophyy". F1000Research. 8: 1621. doi:10.12688/f1000research.19139.1. PMC 6743252. PMID 31559011。
^ Canettieri, G., Koo, S.-H., Berdeaux, R., Heredia, J., Hedrick, S., Zhang, X., & Montminy (2005). “Dual role of the coactivator TORC2 in modulating hepatic glucose output and insulin signaling”. Cell Metabolism 2 (5): 331–338. doi:10.1016/j.cmet.2005.09.008. PMID 16271533.
^ Yoon, J. Cliff; Puigserver, Pere; Chen, Guoxun; Donovan, Jerry; Wu, Zhidan; Rhee, James; Adelmant, Guillaume; Stafford, John et al. (September 2001). “Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1” (英語). Nature 413 (6852): 131–138. Bibcode: 2001Natur.413..131Y. doi:10.1038/35093050. ISSN 1476-4687. PMID 11557972.
^ Liang H, Ward WF (December 2006). "PGC-1alpha: a key regulator of energy metabolism". Adv Physiol Educ. 30 (4): 145–51. doi:10.1152/advan.00052.2006. PMID 17108241。
^ Summermatter S, Santos G, Pérez-Schindler J, Handschin C (May 2013). "Skeletal muscle PGC-1α controls whole-body lactate homeostasis through estrogen-related receptor α-dependent activation of LDH B and repression of LDH A". Proc. Natl. Acad. Sci. U.S.A. 110 (21): 8738–43. Bibcode:2013PNAS..110.8738S. doi:10.1073/pnas.1212976110. PMC 3666691. PMID 23650363。
^ Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P (March 2005). "Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1". Nature. 434 (7029): 113–8. Bibcode:2005Natur.434..113R. doi:10.1038/nature03354. PMID 15744310. S2CID 4380393。
^ Romanino K, Mazelin L, Albert V, Conjard-Duplany A, Lin S, Bentzinger CF, Handschin C, Puigserver P, Zorzato F, Schaeffer L, Gangloff YG, Rüegg MA (December 2011). "Myopathy caused by mammalian target of rapamycin complex 1 (mTORC1) inactivation is not reversed by restoring mitochondrial function". Proc. Natl. Acad. Sci. U.S.A. 108 (51): 20808–13. Bibcode:2011PNAS..10820808R. doi:10.1073/pnas.1111448109. PMC 3251091. PMID 22143799。
^ Summermatter S, Thurnheer R, Santos G, Mosca B, Baum O, Treves S, Hoppeler H, Zorzato F, Handschin C (January 2012). "Remodeling of calcium handling in skeletal muscle through PGC-1α: impact on force, fatigability, and fiber type". Am. J. Physiol., Cell Physiol. 302 (1): C88–99. doi:10.1152/ajpcell.00190.2011. PMID 21918181。
^ Viatour P, Merville MP, Bours V, Chariot A (January 2005). "Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation". Trends Biochem. Sci. 30 (1): 43–52. doi:10.1016/j.tibs.2004.11.009. PMID 15653325。
^ Harris CD, Ermak G, Davies KJ (November 2005). "Multiple roles of the DSCR1 (Adapt78 or RCAN1) gene and its protein product calcipressin 1 (or RCAN1) in disease". Cell. Mol. Life Sci. 62 (21): 2477–86. doi:10.1007/s00018-005-5085-4. PMID 16231093. S2CID 7184948。
^ Olesen J, Larsson S, Iversen N, Yousafzai S, Hellsten Y, Pilegaard H (2012). Calbet JA (ed.). "Skeletal muscle PGC-1α is required for maintaining an acute LPS-induced TNFα response". PLOS ONE. 7 (2): e32222. Bibcode:2012PLoSO...732222O. doi:10.1371/journal.pone.0032222. PMC 3288087. PMID 22384185。
^ Brault JJ, Jespersen JG, Goldberg AL (June 2010). "Peroxisome proliferator-activated receptor gamma coactivator 1alpha or 1beta overexpression inhibits muscle protein degradation, induction of ubiquitin ligases, and disuse atrophy". J. Biol. Chem. 285 (25): 19460–71. doi:10.1074/jbc.M110.113092. PMC 2885225. PMID 20404331。
^ Tran MT, Zsengeller ZK, Berg AH, Khankin EV, Bhasin MK, Kim W, Clish CB, Stillman IE, Karumanchi SA, Rhee EP, Parikh SM (2016). "PGC1α drives NAD biosynthesis linking oxidative metabolism to renal protection". Nature. 531 (7595): 528–32. Bibcode:2016Natur.531..528T. doi:10.1038/nature17184. PMC 4909121. PMID 26982719。
^ Zheng B, Liao Z, Locascio JJ, Lesniak KA, Roderick SS, Watt ML, Eklund AC, Zhang-James Y, Kim PD, Hauser MA, Grünblatt E, Moran LB, Mandel SA, Riederer P, Miller RM, Federoff HJ, Wüllner U, Papapetropoulos S, Youdim MB, Cantuti-Castelvetri I, Young AB, Vance JM, Davis RL, Hedreen JC, Adler CH, Beach TG, Graeber MB, Middleton FA, Rochet JC, Scherzer CR (October 2010). "PGC-1{alpha}, A Potential Therapeutic Target for Early Intervention in Parkinson's Disease". Sci Transl Med. 2 (52): 52ra73. doi:10.1126/scitranslmed.3001059. PMC 3129986. PMID 20926834。
^ Soyal SM, Felder TK, Auer S, Hahne P, Oberkofler H, Witting A, Paulmichl M, Landwehrmeyer GB, Weydt P, Patsch W (2012). "A greatly extended PPARGC1A genomic locus encodes several new brain-specific isoforms and influences Huntington disease age of onset". Human Molecular Genetics. 21 (15): 3461–73. doi:10.1093/hmg/dds177. PMID 22589246。
^ Eschbach J, Schwalenstöcker B, Soyal SM, Bayer H, Wiesner D, Akimoto C, Nilsson AC, Birve A, Meyer T, Dupuis L, Danzer KM, Andersen PM, Witting A, Ludolph AC, Patsch W, Weydt P (2013). "PGC-1α is a male-specific disease modifier of human and experimental amyotrophic lateral sclerosis". Human Molecular Genetics. 22 (17): 3477–84. doi:10.1093/hmg/ddt202. PMID 23669350。
^ Crane JD, Ogborn DI, Cupido C, Melov S, Hubbard A, Bourgeois JM, Tarnopolsky MA (February 2012). "Massage therapy attenuates inflammatory signaling after exercise-induced muscle damage". Sci Transl Med. 4 (119): 119ra13. doi:10.1126/scitranslmed.3002882. PMID 22301554. S2CID 2610669。
^ Brown E (2012年2月1日). “Study works out kinks in understanding of massage”. Los Angeles Times
^ “Videos | The Buck Institute for Research on Aging”. Buckinstitute.org. 2013年10月11日閲覧。
^ Vats D, Mukundan L, Odegaard JI, Zhang L, Smith KL, Morel CR, Wagner RA, Greaves DR, Murray PJ, Chawla A (July 2006). "Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation". Cell Metab. 4 (1): 13–24. doi:10.1016/j.cmet.2006.05.011. PMC 1904486. PMID 16814729。
^ Roberts LD, Boström P, O'Sullivan JF, Schinzel RT, Lewis GD, Dejam A, Lee YK, Palma MJ, Calhoun S, Georgiadi A, Chen MH, Ramachandran VS, Larson MG, Bouchard C, Rankinen T, Souza AL, Clish CB, Wang TJ, Estall JL, Soukas AA, Cowan CA, Spiegelman BM, Gerszten RE (2014). "β-Aminoisobutyric acid induces browning of white fat and hepatic β-oxidation and is inversely correlated with cardiometabolic risk factors". Cell Metabolism. 19 (1): 96–108. doi:10.1016/j.cmet.2013.12.003. PMC 4017355. PMID 24411942。
^ ^a ^b Puigserver P, Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, Spiegelman BM (November 1999). "Activation of PPARgamma coactivator-1 through transcription factor docking". Science. 286 (5443): 1368–71. doi:10.1126/science.286.5443.1368. PMID 10558993。
^ Schreiber SN, Emter R, Hock MB, Knutti D, Cardenas J, Podvinec M, et al. (April 2004). "The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis". Proceedings of the National Academy of Sciences of the United States of America. 101 (17): 6472–7. Bibcode:2004PNAS..101.6472S. doi:10.1073/pnas.0308686101. PMC 404069. PMID 15087503。
^ Zhang Y, Castellani LW, Sinal CJ, Gonzalez FJ, Edwards PA (January 2004). "Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) regulates triglyceride metabolism by activation of the nuclear receptor FXR". Genes Dev. 18 (2): 157–69. doi:10.1101/gad.1138104. PMC 324422. PMID 14729567。
^ Olson BL, Hock MB, Ekholm-Reed S, Wohlschlegel JA, Dev KK, Kralli A, Reed SI (January 2008). "SCFCdc4 acts antagonistically to the PGC-1α transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis". Genes Dev. 22 (2): 252–64. doi:10.1101/gad.1624208. PMC 2192758. PMID 18198341。
^ ^a ^b ^c ^d ^e Wallberg AE, Yamamura S, Malik S, Spiegelman BM, Roeder RG (November 2003). "Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha". Mol. Cell. 12 (5): 1137–49. doi:10.1016/S1097-2765(03)00391-5. PMID 14636573。
^ Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM (1999). "Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1". Cell. 98 (1): 115–24. doi:10.1016/S0092-8674(00)80611-X. PMID 10412986. S2CID 16143809。
^ Delerive P, Wu Y, Burris TP, Chin WW, Suen CS (February 2002). "PGC-1 functions as a transcriptional coactivator for the retinoid X receptors". J. Biol. Chem. 277 (6): 3913–7. doi:10.1074/jbc.M109409200. PMID 11714715。
^ Wu Y, Delerive P, Chin WW, Burris TP (March 2002). "Requirement of helix 1 and the AF-2 domain of the thyroid hormone receptor for coactivation by PGC-1". J. Biol. Chem. 277 (11): 8898–905. doi:10.1074/jbc.M110761200. PMID 11751919。

外部リンク

PPARGC1A protein, human - MeSH・アメリカ国立医学図書館・生命科学用語シソーラス（英語）
FactorBook PGC1A
Overview of all the structural information available in the PDB for UniProt: Q9UBK2 (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha) at the PDBe-KB.

[refGRCm38Ensembl-1] GRCm38: Ensembl release 89: ENSMUSG00000029167 - Ensembl, May 2017

[2] Human PubMed Reference:

[3] Mouse PubMed Reference:

[pmid10585775-4] Esterbauer H, Oberkofler H, Krempler F, Patsch W (February 2000). "Human peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene: cDNA sequence, genomic organization, chromosomal localization, and tissue expression". Genomics. 62 (1): 98–102. doi:10.1006/geno.1999.5977. PMID 10585775。

[pmid16915236-5] Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M, Vanderhaeghen P, Haussler D (September 2006). "An RNA gene expressed during cortical development evolved rapidly in humans". Nature. 443 (7108): 167–72. Bibcode:2006Natur.443..167P. doi:10.1038/nature05113. PMID 16915236. S2CID 18107797。

[Mitochondrial_biogenesis-6] Valero T (2014). "Mitochondrial biogenesis: pharmacological approaches". Curr. Pharm. Des. 20 (35): 5507–9. doi:10.2174/138161282035140911142118. hdl:10454/13341. PMID 24606795. Mitochondrial biogenesis is therefore defined as the process via which cells increase their individual mitochondrial mass [3]. ... This work reviews different strategies to enhance mitochondrial bioenergetics in order to ameliorate the neurodegenerative process, with an emphasis on clinical trials reports that indicate their potential. Among them creatine, Coenzyme Q10 and mitochondrial targeted antioxidants/peptides are reported to have the most remarkable effects in clinical trials.

[Mitochondrial_biogenesis_in_health_and_disease-7] Sanchis-Gomar F, García-Giménez JL, Gómez-Cabrera MC, Pallardó FV (2014). "Mitochondrial biogenesis in health and disease. Molecular and therapeutic approaches". Curr. Pharm. Des. 20 (35): 5619–5633. doi:10.2174/1381612820666140306095106. PMID 24606801. Mitochondrial biogenesis (MB) is the essential mechanism by which cells control the number of mitochondria.

[pmid26443844-8] Dorn GW, Vega RB, Kelly DP (2015). "Mitochondrial biogenesis and dynamics in the developing and diseased heart". Genes Dev. 29 (19): 1981–91. doi:10.1101/gad.269894.115. PMC 4604339. PMID 26443844。

[pmid32518153-9] Klein MA, Denu JM (2020). "Biological and catalytic functions of sirtuin 6 as targets for small-molecule modulators". Journal of Biological Chemistry. 295 (32): 11021–11041. doi:10.1074/jbc.REV120.011438. PMC 7415977. PMID 32518153。

[:0-10] “PPARGC1A PPARG coactivator 1 alpha [Homo sapiens (human) - Gene - NCBI]”. www.ncbi.nlm.nih.gov. 2022年3月5日閲覧。

[pmid12181572-11] Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O, Michael LF, Puigserver P, Isotani E, Olson EN, Lowell BB, Bassel-Duby R, Spiegelman BM (2002). "Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres". Nature. 418 (6899): 797–801. Bibcode:2002Natur.418..797L. doi:10.1038/nature00904. PMID 12181572. S2CID 4415526。

[pmid12563009-12] Pilegaard H, Saltin B, Neufer PD (February 2003). "Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle". J. Physiol. 546 (Pt 3): 851–8. doi:10.1113/jphysiol.2002.034850. PMC 2342594. PMID 12563009。

[pmid25673772-13] Vainshtein A, Tryon LD, Pauly M, Hood DA (2015). "Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle". American Journal of Physiology. 308 (9): C710-719. doi:10.1152/ajpcell.00380.2014. PMC 4420796. PMID 25673772。

[pmid21284983-14] Wu J, Ruas JL, Estall JL, Rasbach KA, Choi JH, Ye L, Boström P, Tyra HM, Crawford RW, Campbell KP, Rutkowski DT, Kaufman RJ, Spiegelman BM (2011). "The unfolded protein response mediates adaptation to exercise in skeletal muscle through a PGC-1α/ATF6α complex". Cell Metabolism. 13 (2): 160–169. doi:10.1016/j.cmet.2011.01.003. PMC 3057411. PMID 21284983。

[pmid31559011-15] Ji LL, Yeo D (2019). "Mitochondrial dysregulation and muscle disuse atrophyy". F1000Research. 8: 1621. doi:10.12688/f1000research.19139.1. PMC 6743252. PMID 31559011。

[:1-16] Canettieri, G., Koo, S.-H., Berdeaux, R., Heredia, J., Hedrick, S., Zhang, X., & Montminy (2005). “Dual role of the coactivator TORC2 in modulating hepatic glucose output and insulin signaling”. Cell Metabolism 2 (5): 331–338. doi:10.1016/j.cmet.2005.09.008. PMID 16271533.

[:2-17] Yoon, J. Cliff; Puigserver, Pere; Chen, Guoxun; Donovan, Jerry; Wu, Zhidan; Rhee, James; Adelmant, Guillaume; Stafford, John et al. (September 2001). “Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1” (英語). Nature 413 (6852): 131–138. Bibcode: 2001Natur.413..131Y. doi:10.1038/35093050. ISSN 1476-4687. PMID 11557972.

[pmid17108241-18] Liang H, Ward WF (December 2006). "PGC-1alpha: a key regulator of energy metabolism". Adv Physiol Educ. 30 (4): 145–51. doi:10.1152/advan.00052.2006. PMID 17108241。

[pmid23650363-19] Summermatter S, Santos G, Pérez-Schindler J, Handschin C (May 2013). "Skeletal muscle PGC-1α controls whole-body lactate homeostasis through estrogen-related receptor α-dependent activation of LDH B and repression of LDH A". Proc. Natl. Acad. Sci. U.S.A. 110 (21): 8738–43. Bibcode:2013PNAS..110.8738S. doi:10.1073/pnas.1212976110. PMC 3666691. PMID 23650363。

[pmid15744310-20] Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P (March 2005). "Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1". Nature. 434 (7029): 113–8. Bibcode:2005Natur.434..113R. doi:10.1038/nature03354. PMID 15744310. S2CID 4380393。

[pmid22143799-21] Romanino K, Mazelin L, Albert V, Conjard-Duplany A, Lin S, Bentzinger CF, Handschin C, Puigserver P, Zorzato F, Schaeffer L, Gangloff YG, Rüegg MA (December 2011). "Myopathy caused by mammalian target of rapamycin complex 1 (mTORC1) inactivation is not reversed by restoring mitochondrial function". Proc. Natl. Acad. Sci. U.S.A. 108 (51): 20808–13. Bibcode:2011PNAS..10820808R. doi:10.1073/pnas.1111448109. PMC 3251091. PMID 22143799。

[pmid21918181-22] Summermatter S, Thurnheer R, Santos G, Mosca B, Baum O, Treves S, Hoppeler H, Zorzato F, Handschin C (January 2012). "Remodeling of calcium handling in skeletal muscle through PGC-1α: impact on force, fatigability, and fiber type". Am. J. Physiol., Cell Physiol. 302 (1): C88–99. doi:10.1152/ajpcell.00190.2011. PMID 21918181。

[pmid15653325-23] Viatour P, Merville MP, Bours V, Chariot A (January 2005). "Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation". Trends Biochem. Sci. 30 (1): 43–52. doi:10.1016/j.tibs.2004.11.009. PMID 15653325。

[pmid16231093-24] Harris CD, Ermak G, Davies KJ (November 2005). "Multiple roles of the DSCR1 (Adapt78 or RCAN1) gene and its protein product calcipressin 1 (or RCAN1) in disease". Cell. Mol. Life Sci. 62 (21): 2477–86. doi:10.1007/s00018-005-5085-4. PMID 16231093. S2CID 7184948。

[pmid22384185-25] Olesen J, Larsson S, Iversen N, Yousafzai S, Hellsten Y, Pilegaard H (2012). Calbet JA (ed.). "Skeletal muscle PGC-1α is required for maintaining an acute LPS-induced TNFα response". PLOS ONE. 7 (2): e32222. Bibcode:2012PLoSO...732222O. doi:10.1371/journal.pone.0032222. PMC 3288087. PMID 22384185。

[pmid20404331-26] Brault JJ, Jespersen JG, Goldberg AL (June 2010). "Peroxisome proliferator-activated receptor gamma coactivator 1alpha or 1beta overexpression inhibits muscle protein degradation, induction of ubiquitin ligases, and disuse atrophy". J. Biol. Chem. 285 (25): 19460–71. doi:10.1074/jbc.M110.113092. PMC 2885225. PMID 20404331。

[pmid26982719-27] Tran MT, Zsengeller ZK, Berg AH, Khankin EV, Bhasin MK, Kim W, Clish CB, Stillman IE, Karumanchi SA, Rhee EP, Parikh SM (2016). "PGC1α drives NAD biosynthesis linking oxidative metabolism to renal protection". Nature. 531 (7595): 528–32. Bibcode:2016Natur.531..528T. doi:10.1038/nature17184. PMC 4909121. PMID 26982719。

[pmid20926834-28] Zheng B, Liao Z, Locascio JJ, Lesniak KA, Roderick SS, Watt ML, Eklund AC, Zhang-James Y, Kim PD, Hauser MA, Grünblatt E, Moran LB, Mandel SA, Riederer P, Miller RM, Federoff HJ, Wüllner U, Papapetropoulos S, Youdim MB, Cantuti-Castelvetri I, Young AB, Vance JM, Davis RL, Hedreen JC, Adler CH, Beach TG, Graeber MB, Middleton FA, Rochet JC, Scherzer CR (October 2010). "PGC-1{alpha}, A Potential Therapeutic Target for Early Intervention in Parkinson's Disease". Sci Transl Med. 2 (52): 52ra73. doi:10.1126/scitranslmed.3001059. PMC 3129986. PMID 20926834。

[pmid22589246-29] Soyal SM, Felder TK, Auer S, Hahne P, Oberkofler H, Witting A, Paulmichl M, Landwehrmeyer GB, Weydt P, Patsch W (2012). "A greatly extended PPARGC1A genomic locus encodes several new brain-specific isoforms and influences Huntington disease age of onset". Human Molecular Genetics. 21 (15): 3461–73. doi:10.1093/hmg/dds177. PMID 22589246。

[Patsch18-30] Eschbach J, Schwalenstöcker B, Soyal SM, Bayer H, Wiesner D, Akimoto C, Nilsson AC, Birve A, Meyer T, Dupuis L, Danzer KM, Andersen PM, Witting A, Ludolph AC, Patsch W, Weydt P (2013). "PGC-1α is a male-specific disease modifier of human and experimental amyotrophic lateral sclerosis". Human Molecular Genetics. 22 (17): 3477–84. doi:10.1093/hmg/ddt202. PMID 23669350。

[pmid22301554-31] Crane JD, Ogborn DI, Cupido C, Melov S, Hubbard A, Bourgeois JM, Tarnopolsky MA (February 2012). "Massage therapy attenuates inflammatory signaling after exercise-induced muscle damage". Sci Transl Med. 4 (119): 119ra13. doi:10.1126/scitranslmed.3002882. PMID 22301554. S2CID 2610669。

[:3-32] Brown E (2012年2月1日). “Study works out kinks in understanding of massage”. Los Angeles Times

[:4-33] “Videos | The Buck Institute for Research on Aging”. Buckinstitute.org. 2013年10月11日閲覧。

[pmid16814729-34] Vats D, Mukundan L, Odegaard JI, Zhang L, Smith KL, Morel CR, Wagner RA, Greaves DR, Murray PJ, Chawla A (July 2006). "Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation". Cell Metab. 4 (1): 13–24. doi:10.1016/j.cmet.2006.05.011. PMC 1904486. PMID 16814729。

[pmid24411942-35] Roberts LD, Boström P, O'Sullivan JF, Schinzel RT, Lewis GD, Dejam A, Lee YK, Palma MJ, Calhoun S, Georgiadi A, Chen MH, Ramachandran VS, Larson MG, Bouchard C, Rankinen T, Souza AL, Clish CB, Wang TJ, Estall JL, Soukas AA, Cowan CA, Spiegelman BM, Gerszten RE (2014). "β-Aminoisobutyric acid induces browning of white fat and hepatic β-oxidation and is inversely correlated with cardiometabolic risk factors". Cell Metabolism. 19 (1): 96–108. doi:10.1016/j.cmet.2013.12.003. PMC 4017355. PMID 24411942。

[pmid10558993-36] Puigserver P, Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, Spiegelman BM (November 1999). "Activation of PPARgamma coactivator-1 through transcription factor docking". Science. 286 (5443): 1368–71. doi:10.1126/science.286.5443.1368. PMID 10558993。

[37] Schreiber SN, Emter R, Hock MB, Knutti D, Cardenas J, Podvinec M, et al. (April 2004). "The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis". Proceedings of the National Academy of Sciences of the United States of America. 101 (17): 6472–7. Bibcode:2004PNAS..101.6472S. doi:10.1073/pnas.0308686101. PMC 404069. PMID 15087503。

[pmid14729567-38] Zhang Y, Castellani LW, Sinal CJ, Gonzalez FJ, Edwards PA (January 2004). "Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) regulates triglyceride metabolism by activation of the nuclear receptor FXR". Genes Dev. 18 (2): 157–69. doi:10.1101/gad.1138104. PMC 324422. PMID 14729567。

[pmid18198341-39] Olson BL, Hock MB, Ekholm-Reed S, Wohlschlegel JA, Dev KK, Kralli A, Reed SI (January 2008). "SCFCdc4 acts antagonistically to the PGC-1α transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis". Genes Dev. 22 (2): 252–64. doi:10.1101/gad.1624208. PMC 2192758. PMID 18198341。

[pmid14636573-40] Wallberg AE, Yamamura S, Malik S, Spiegelman BM, Roeder RG (November 2003). "Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha". Mol. Cell. 12 (5): 1137–49. doi:10.1016/S1097-2765(03)00391-5. PMID 14636573。

[pmid10412986-41] Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM (1999). "Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1". Cell. 98 (1): 115–24. doi:10.1016/S0092-8674(00)80611-X. PMID 10412986. S2CID 16143809。

[pmid11714715-42] Delerive P, Wu Y, Burris TP, Chin WW, Suen CS (February 2002). "PGC-1 functions as a transcriptional coactivator for the retinoid X receptors". J. Biol. Chem. 277 (6): 3913–7. doi:10.1074/jbc.M109409200. PMID 11714715。

[pmid11751919-43] Wu Y, Delerive P, Chin WW, Burris TP (March 2002). "Requirement of helix 1 and the AF-2 domain of the thyroid hormone receptor for coactivation by PGC-1". J. Biol. Chem. 277 (11): 8898–905. doi:10.1074/jbc.M110761200. PMID 11751919。

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[23]

[24]

[25]

[26]

[27]

[28]

[29]

[30]

[31]

[32]

[33]

[34]

[35]

[36]

[37]

[38]

[39]

[40]

[41]

[42]

[43]

PPARGC1A

機能

調節

臨床的意義

相互作用

出典

関連文献

関連項目

外部リンク