[HTML][HTML] Peroxisome proliferator–activated receptor γ coactivator-1 promotes cardiac mitochondrial biogenesis

JJ Lehman, PM Barger, A Kovacs… - The Journal of …, 2000 - Am Soc Clin Investig
JJ Lehman, PM Barger, A Kovacs, JE Saffitz, DM Medeiros, DP Kelly
The Journal of clinical investigation, 2000Am Soc Clin Investig
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 γ 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 …
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 γ 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.
The Journal of Clinical Investigation