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Transcriptional coactivators PGC-1alpha and PGC-lbeta control overlapping programs required for perinatal maturation of the heart.

Genes & development | Jul 15, 2008

http://www.ncbi.nlm.nih.gov/pubmed/18628400

Oxidative tissues such as heart undergo a dramatic perinatal mitochondrial biogenesis to meet the high-energy demands after birth. PPARgamma coactivator-1 (PGC-1) alpha and beta have been implicated in the transcriptional control of cellular energy metabolism. Mice with combined deficiency of PGC-1alpha and PGC-1beta (PGC-1alphabeta(-/-) mice) were generated to investigate the convergence of their functions in vivo. The phenotype of PGC-1beta(-/-) mice was minimal under nonstressed conditions, including normal heart function, similar to that of PGC-1alpha(-/-) mice generated previously. In striking contrast to the singly deficient PGC-1 lines, PGC-1alphabeta(-/-) mice died shortly after birth with small hearts, bradycardia, intermittent heart block, and a markedly reduced cardiac output. Cardiac-specific ablation of the PGC-1beta gene on a PGC-1alpha-deficient background phenocopied the generalized PGC-1alphabeta(-/-) mice. The hearts of the PGC-1alphabeta(-/-) mice exhibited signatures of a maturational defect including reduced growth, a late fetal arrest in mitochondrial biogenesis, and persistence of a fetal pattern of gene expression. Brown adipose tissue (BAT) of PGC-1alphabeta(-/-) mice also exhibited a severe abnormality in function and mitochondrial density. We conclude that PGC-1alpha and PGC-1beta share roles that collectively are necessary for the postnatal metabolic and functional maturation of heart and BAT.

Pubmed ID: 18628400 RIS Download

Mesh terms: Adipose Tissue, Brown | Animals | Blotting, Southern | Female | Gene Expression Profiling | Heart | Integrases | Male | Mice | Mice, Inbred C57BL | Mice, Knockout | Mitochondria, Heart | Oligonucleotide Array Sequence Analysis | Polymerase Chain Reaction | Trans-Activators | Transcription Factors

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Associated grants

  • Agency: NCI NIH HHS, Id: P30 CA91842
  • Agency: NIDDK NIH HHS, Id: P30 DK056341
  • Agency: NIDDK NIH HHS, Id: P30 DK056341-07
  • Agency: NIDDK NIH HHS, Id: P30 DK056341-08
  • Agency: NIDDK NIH HHS, Id: P30 DK56341
  • Agency: NIDDK NIH HHS, Id: P30DK052574
  • Agency: NIDDK NIH HHS, Id: P60 DK020579
  • Agency: NIDDK NIH HHS, Id: R01 DK045416
  • Agency: NHLBI NIH HHS, Id: R01 HL058427

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