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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAjY5jAdbiRuX202B_gd_MTN6jM8qunr1fIHpoRXo5CzE#_7 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RAjY5jAdbiRuX202B_gd_MTN6jM8qunr1fIHpoRXo5CzE#_6 http://www.w3.org/ns/prov#value (27), who showed that forced expression of PGC-1 in cardiac myocytes induced a large increase in mitochondria with tightly coupled respiration. The finding that PGC-1 controls GLUT4 gene expression helps explain the mechanisms underlying the coordinate regulation of mitochondrial biogenesis and GLUT4 expression in response to various stimuli. Besides exercise, these include hyperthyroidism (42, 43), lowering of muscle ATP and phosphocreatine levels by creatine depletion (44), and activation of AMP kinase (45, 46). Activation of AMP kinase appears to be the mechanism by which exercise stimulates muscle glucose transport (47-49). Stimulated muscle glucose transport is normally proportional to the muscles' GLUT4 content (17, 50, 51). Thus, PGC-1 coordinately regulates the capacity of muscle to take up glucose and to oxidize it. Mitochondria contain their own genome, which encodes 13 of the 100 proteins that make up the enzyme complexes of the respiratory electron transport chain (52). The others are products of nuclear genes. Nuclear genes also provide the factors that regulate mitochondrial DNA transcription and replication, and they encode enzymes of the citrate cycle and of fatty acid and ketone oxidation. A fundamental question is, How is the transcription of nuclear and mitochondrial genes coordinated during both steady-state conditions and adaptive responses to changes in energy demand? Scarpulla and co-workers (21-23) have identified two transcription factors, NRF-1 and NRF-2, that appear to play a major role in this integrative function. Functional recognition sites for one or both of these transcription factors have been identified in the promoters of nuclear genes that encode subunits of the respiratory chain enzyme complexes, some of the mitochondrial matrix enzymes, and mtDNA transcription and replication factors (21-24, 53, 54). PGC-1 has been shown to coactivate NRF-1, to increase NRF-1 and NRF-2 gene expression, and to stimulate mitochondrial biogenesis (26). In light of the results of this study, it seems probable that increased expression of PGC-1, acting in concert with increases in NRF-1 and NRF-2, plays a major role in stimulating mitochondrial biogenesis by exercise. http://www.tkuhn.ch/bel2nanopub/RAjY5jAdbiRuX202B_gd_MTN6jM8qunr1fIHpoRXo5CzE#_6 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/12468452 http://www.tkuhn.ch/bel2nanopub/RAjY5jAdbiRuX202B_gd_MTN6jM8qunr1fIHpoRXo5CzE#_7 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAjY5jAdbiRuX202B_gd_MTN6jM8qunr1fIHpoRXo5CzE#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/12468452 http://www.tkuhn.ch/bel2nanopub/RAjY5jAdbiRuX202B_gd_MTN6jM8qunr1fIHpoRXo5CzE#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAjY5jAdbiRuX202B_gd_MTN6jM8qunr1fIHpoRXo5CzE#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAjY5jAdbiRuX202B_gd_MTN6jM8qunr1fIHpoRXo5CzE#_6 http://www.tkuhn.ch/bel2nanopub/RAjY5jAdbiRuX202B_gd_MTN6jM8qunr1fIHpoRXo5CzE#pubinfo http://www.tkuhn.ch/bel2nanopub/RAjY5jAdbiRuX202B_gd_MTN6jM8qunr1fIHpoRXo5CzE http://purl.org/dc/terms/created 2014-07-03T14:30:07.694+02:00 http://www.tkuhn.ch/bel2nanopub/RAjY5jAdbiRuX202B_gd_MTN6jM8qunr1fIHpoRXo5CzE http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAjY5jAdbiRuX202B_gd_MTN6jM8qunr1fIHpoRXo5CzE http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234