Defects in energy homeostasis in Leigh syndrome French Canadian variant through PGC-1α/LRP130 complex Journal Article
| Authors: | Cooper, M. P.; Qu, L.; Rohas, L. M.; Lin, J.; Yang, W.; Erdjument-Bromage, H.; Tempst, P.; Spiegelman, B. M. |
| Article Title: | Defects in energy homeostasis in Leigh syndrome French Canadian variant through PGC-1α/LRP130 complex |
| Abstract: | Leigh syndrome French Canadian variant (LSFC) is an autosomal recessive neurodegenerative disorder due to mutation in the LRP130 (leucine-rich protein 130 kDa) gene. Unlike classic Leigh syndrome, the French Canadian variant spares the heart, skeletal muscle, and kidneys, but severely affects the liver. The precise role of LRP130 in cytochrome c oxidase deficiency and hepatic lactic acidosis that accompanies this disorder is unknown. We show here that LRP130 is a component of the PGC-1α (peroxisome proliferator-activated receptor coactivator 1-α) transcriptional coactivator holocomplex and regulates expression of PEPCK (phosphoenolpyruvate carboxykinase), G6P (glucose-6-phosphatase), and certain mitochondrial genes through PGC-1α. Reduction of LRP130 in fasted mice via adenoviral RNA interference (RNAi) vector blocks the induction of PEPCK and G6P, and blunts hepatic glucose output. LRP130 is also necessary for PGC-1α-dependent transcription of several mitochondrial genes in vivo. These data link LRP130 and PGC-1α to defective hepatic energy homeostasis in LSFC, and reveal a novel regulatory mechanism of glucose homeostasis. © 2006 by Cold Spring Harbor Laboratory Press. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; nonhuman; forkhead transcription factors; animal cell; mouse; animals; mice; animal tissue; protein protein interaction; neoplasm proteins; animal experiment; animal model; rna interference; genetic transcription; in vivo study; rna binding protein; gene expression regulation; liver; chromatin; chromatin immunoprecipitation; binding site; gene control; glucose; binding sites; trans-activators; adenovirus vector; homeostasis; energy metabolism; mitochondrion; diet restriction; enzyme induction; energy balance; nucleic acid binding protein; gluconeogenesis; peroxisome proliferator activated receptor gamma coactivator 1alpha; leigh syndrome french canadian variant; leigh syndrome; lprprc; lrp130; pgc-1α; glucose 6 phosphatase; phosphoenolpyruvate carboxykinase (gtp); protein fox01; protein lrp130; leigh disease; genes, mitochondrial; glucose-6-phosphatase; phosphoenolpyruvate carboxykinase (atp) |
| Journal Title: | Genes and Development |
| Volume: | 20 |
| Issue: | 21 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2006-11-01 |
| Start Page: | 2996 |
| End Page: | 3009 |
| Language: | English |
| DOI: | 10.1101/gad.1483906 |
| PUBMED: | 17050673 |
| PROVIDER: | scopus |
| PMCID: | PMC1620022 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 33" - "Export Date: 4 June 2012" - "CODEN: GEDEE" - "Source: Scopus" |
