| First Author | Lai L | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 4 | Pages | 2250-9 |
| PubMed ID | 24337569 | Mgi Jnum | J:209523 |
| Mgi Id | MGI:5568032 | Doi | 10.1074/jbc.M113.523654 |
| Citation | Lai L, et al. (2014) A role for peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1) in the regulation of cardiac mitochondrial phospholipid biosynthesis. J Biol Chem 289(4):2250-9 |
| abstractText | The energy demands of the adult mammalian heart are met largely by ATP generated via oxidation of fatty acids in a high capacity mitochondrial system. Peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1)-alpha and -beta serve as inducible transcriptional coregulators of genes involved in mitochondrial biogenesis and metabolism. Whether PGC-1 plays a role in the regulation of mitochondrial structure is unknown. In this study, mice with combined deficiency of PGC-1alpha and PGC-1beta (PGC-1alphabeta(-/-)) in adult heart were analyzed. PGC-1alphabeta(-/-) hearts exhibited a distinctive mitochondrial cristae-stacking abnormality suggestive of a phospholipid abnormality as has been described in humans with genetic defects in cardiolipin (CL) synthesis (Barth syndrome). A subset of molecular species, containing n-3 polyunsaturated species in the CL, phosphatidylcholine, and phosphatidylethanolamine profiles, was reduced in PGC-1alphabeta-deficient hearts. Gene expression profiling of PGC-1alphabeta(-/-) hearts revealed reduced expression of the gene encoding CDP-diacylglycerol synthase 1 (Cds1), an enzyme that catalyzes the proximal step in CL biosynthesis. Cds1 gene promoter-reporter cotransfection experiments and chromatin immunoprecipitation studies demonstrated that PGC-1alpha coregulates estrogen-related receptors to activate the transcription of the Cds1 gene. We conclude that the PGC-1/estrogen-related receptor axis coordinately regulates metabolic and membrane structural programs relevant to the maintenance of high capacity mitochondrial function in heart. |
