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Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis.

Cardiac mitochondrial function is altered in a variety of inherited and acquired cardiovascular diseases. Recent studies have identified the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) as a regulator of mitochondrial function in tissues specialized for thermogenesis, such as brown adipose. We sought to determine whether PGC-1 controlled mitochondrial biogenesis and energy-producing capacity in the heart, a tissue specialized for high-capacity ATP production. We found that PGC-1 gene expression is induced in the mouse heart after birth and in response to short-term fasting, conditions known to increase cardiac mitochondrial energy production. Forced expression of PGC-1 in cardiac myocytes in culture induced the expression of nuclear and mitochondrial genes involved in multiple mitochondrial energy-transduction/energy-production pathways, increased cellular mitochondrial number, and stimulated coupled respiration. Cardiac-specific overexpression of PGC-1 in transgenic mice resulted in uncontrolled mitochondrial proliferation in cardiac myocytes leading to loss of sarcomeric structure and a dilated cardiomyopathy. These results identify PGC-1 as a critical regulatory molecule in the control of cardiac mitochondrial number and function in response to energy demands.

Pubmed ID: 11018072

Authors

  • Lehman JJ
  • Barger PM
  • Kovacs A
  • Saffitz JE
  • Medeiros DM
  • Kelly DP

Journal

The Journal of clinical investigation

Publication Data

October 30, 2000

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK45416
  • Agency: NHLBI NIH HHS, Id: HL58493
  • Agency: NIDDK NIH HHS, Id: P30DK56341

Mesh Terms

  • Animals
  • Animals, Newborn
  • Cardiomyopathy, Dilated
  • Cell Nucleus
  • Cell Respiration
  • Cells, Cultured
  • Energy Metabolism
  • Fasting
  • Female
  • Gene Expression Regulation
  • Male
  • Mice
  • Mice, Transgenic
  • Mitochondria, Heart
  • Myocardium
  • Transcription Factors