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Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis.
J Clin Invest. 2000 Oct; 106(7):847-56.JCI

Abstract

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.

Authors+Show Affiliations

Department of Medicine, and. Department of Pathology, Center for Cardiovascular Research, Washington University School of Medicine, St. Louis, Missouri 63110, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11018072

Citation

Lehman, J J., et al. "Peroxisome Proliferator-activated Receptor Gamma Coactivator-1 Promotes Cardiac Mitochondrial Biogenesis." The Journal of Clinical Investigation, vol. 106, no. 7, 2000, pp. 847-56.
Lehman JJ, Barger PM, Kovacs A, et al. Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest. 2000;106(7):847-56.
Lehman, J. J., Barger, P. M., Kovacs, A., Saffitz, J. E., Medeiros, D. M., & Kelly, D. P. (2000). Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. The Journal of Clinical Investigation, 106(7), 847-56.
Lehman JJ, et al. Peroxisome Proliferator-activated Receptor Gamma Coactivator-1 Promotes Cardiac Mitochondrial Biogenesis. J Clin Invest. 2000;106(7):847-56. PubMed PMID: 11018072.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. AU - Lehman,J J, AU - Barger,P M, AU - Kovacs,A, AU - Saffitz,J E, AU - Medeiros,D M, AU - Kelly,D P, PY - 2000/10/6/pubmed PY - 2001/2/28/medline PY - 2000/10/6/entrez SP - 847 EP - 56 JF - The Journal of clinical investigation JO - J. Clin. Invest. VL - 106 IS - 7 N2 - 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. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/11018072/Peroxisome_proliferator_activated_receptor_gamma_coactivator_1_promotes_cardiac_mitochondrial_biogenesis_ L2 - https://doi.org/10.1172/JCI10268 DB - PRIME DP - Unbound Medicine ER -