Preferred Label : PGC1a Regulation Pathway;
NCIt related terms : Regulation of PGC-1a;
Alternative definition : BIOCARTA: Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a)
is a tissue-specific coactivator that enhances the activity of many nuclear receptors
and coordinates transcriptional programs important for energy metabolism and energy
homeostasis. Inappropriate increases in PGC-1a activity have been linked to a number
of pathological conditions including heart failure and diabetes. PGC-1a is highly
expressed in metabolically active tissues including brown fat, skeletal muscle and
heart. PGC-1a has been implicated in mitochondrial biogenesis in the heart and increased
mitochondrial respiration in brown fat. PGC-1a is a coactivator for many factors including,
CBP, Scr-1, PPARa, glucocorticoid receptor, thyroid hormone receptor, several orphan
receptors, and MEF2. This pathway illustrates two of the cofactor regulatory factors,
MEF2 and PPARa, and an example orphan receptor feedback inhibition loop. Glut4 is
used as an example of the downstream elements leading to changes in metabolism. Ichida
et al discovered the ERRa repression of PGC-1a. Their results suggest a novel mechanism
of transcriptional control wherein ERR-a can function as a specific molecular repressor
of PGC-1a. This suggests that other co-activators might also have specific repressors,
adding another layer of combinatorial complexity in transcriptional regulation. Czubryt
et al identified PGC-1a as a key target of the MEF2/HDAC regulatory pathway and demonstrated
this pathway's importance in maintenance of cardiac mitochondrial function. The linking
of MEF2/HDAC provides a potential explanation for the increase in mitochondrial number
observed in response to CaMK signaling. (This definition may be outdated - see the
DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_pgc1aPathway;
Origin ID : C39188;
UMLS CUI : C1518790;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
