PPARGC1A (PGC-1α): Master Regulator of Mitochondrial Biogenesis and Metabolic Adaptation
A comprehensive biomedical reference for PPARGC1A, covering gene structure, expression, disease associations, mutations, and functional pathways.
Gene Information Card
| Symbol | PPARGC1A |
|---|---|
| Full Name | PPARGC1A (PPARG coactivator 1 alpha) |
| Gene Type | protein-coding |
| Chromosomal Location | 4p15.2 |
| NCBI Gene ID | 10891 ncbi.nlm.nih.gov/gene/10891 |
| Ensembl ID | ENSG00000109819 |
| UniProt ID | Q9UBK2 |
| OMIM ID | 604517 |
| HGNC ID | 9237 |
| Aliases | PGC1A, PGC-1alpha, PGC-1v, LEM6, PPARGC1 |
Description
PPARGC1A encodes peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a transcriptional coactivator that regulates energy metabolism by promoting mitochondrial biogenesis, oxidative phosphorylation, and adaptive thermogenesis. It interacts with nuclear receptors and transcription factors to coordinate metabolic programs in response to physiological stimuli such as cold exposure, fasting, and exercise.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity and Type 2 Diabetes | Reduced PGC-1α expression in muscle and adipose tissue impairs mitochondrial function and insulin sensitivity, contributing to metabolic dysregulation. | Multiple association studies; PMID: 12538641, 15665756 (via NCBI/OMIM) |
| Neurodegenerative disorders (e.g., Huntington's disease) | PGC-1α downregulation leads to mitochondrial dysfunction and oxidative stress, exacerbating neuronal damage. | Experimental models; PMID: 16814720 (via NCBI/OMIM) |
| Cardiovascular disease | PGC-1α deficiency impairs cardiac mitochondrial function, increasing susceptibility to heart failure under stress. | Animal models; PMID: 15302870 (via NCBI/OMIM) |
| Cancer (e.g., breast, colon) | Altered PGC-1α expression influences tumor metabolism and progression; both oncogenic and tumor-suppressive roles reported depending on context. | COSMIC and literature; PMID: 25860878 (via NCBI/COSMIC) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | High (nTPM ~ 50-100) | High expression; critical for cardiac mitochondrial function |
| Skeletal Muscle | High (nTPM ~ 40-80) | High expression; regulates oxidative capacity and fiber type |
| Liver | Moderate (nTPM ~ 20-40) | Moderate expression; involved in gluconeogenesis and lipid metabolism |
| Adipose Tissue | Moderate (nTPM ~ 15-30) | Moderate expression; regulates thermogenesis and adipocyte differentiation |
| Brain | Low (nTPM ~ 5-15) | Low expression; present in neurons, involved in neuroprotection |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | ~20 | Moderate expression; used in metabolic studies |
| C2C12 (myoblast) | ~30 | High expression upon differentiation; model for muscle metabolism |
| 3T3-L1 (adipocyte) | ~25 | Moderate expression; induced during adipogenesis |
| SH-SY5Y (neuroblastoma) | ~10 | Low expression; used in neurodegeneration studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Gly482Ser (rs8192678) | SNP (missense) | ~30-40% in populations | Associated with altered metabolic traits; reduced coactivator activity in some studies |
| Thr394Thr (rs2970847) | Synonymous SNP | ~20-30% | No known functional effect; used in association studies |
| Various intronic variants | Intronic | Variable | Linked to type 2 diabetes and obesity in some populations; functional impact unclear |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations or reduced expression lead to mitochondrial dysfunction, impaired oxidative metabolism, and increased susceptibility to metabolic and neurodegenerative diseases.
Gain of Function (GOF)
Gain-of-function effects are rare; overexpression in certain cancers may promote metabolic reprogramming and tumor growth, but not due to specific mutations.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported; most variants are hypomorphic or regulatory.
View complete mutation data：
Gene Ontology (GO)
| • transcription coactivator activity (GO:0003713) | • protein binding (GO:0005515) |
| • nuclear receptor binding (GO:0030522) | • mitochondrion (GO:0005739) |
| • regulation of transcription by RNA polymerase II (GO:0006357) | • response to cold (GO:0009409) |
| • cellular response to oxidative stress (GO:0034599) |
Pathways
• AMPK signaling pathway (KEGG: hsa04152)
• PPAR signaling pathway (KEGG: hsa03320)
• Oxidative phosphorylation (KEGG: hsa00190)
• Thermogenesis (KEGG: hsa04714)
• Insulin signaling pathway (KEGG: hsa04910)
Protein Summary
PGC-1α is a 798-amino acid protein with a molecular weight of ~91 kDa. It contains an N-terminal activation domain, a nuclear receptor interaction motif (LXXLL), and a C-terminal RNA recognition motif. It functions as a coactivator for multiple transcription factors, including PPARγ, PPARα, ERRα, and NRF1, thereby regulating genes involved in mitochondrial biogenesis, fatty acid oxidation, and gluconeogenesis. Post-translational modifications (e.g., phosphorylation, acetylation) modulate its activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPARGC1A Knockout HEK293 Cell Line | EDJ-KQ1452 | Human | 10891 | Details Get a Quote |
| PPARGC1A Knockout HeLa Cell Line | EDJ-KQ21008 | Human | 10891 | Details Get a Quote |
| PPARGC1A Knockout A-549 Cell Line | EDJ-KQ64008 | Human | 10891 | Details Get a Quote |
| PPARGC1A Knockout HCT 116 Cell Line | EDJ-KQ72459 | Human | 10891 | Details Get a Quote |
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