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Peroxisome Proliferator-Activated Receptor Coactivator 1 Coactivators, Energy Homeostasis, and Metabolism

Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115

Correspondence: Address all correspondence and requests for reprints to: Bruce M. Spiegelman, Dana-Farber Cancer Institute, One Jimmy Fund Way, Boston, Massachusetts 02115. E-mail: bruce_spiegelman{at}dfci.harvard.edu

Many biological programs are regulated at the transcriptional level. This is generally achieved by the concerted actions of several transcription factors. Recent findings have shown that, in many cases, transcriptional coactivators coordinate the overall regulation of the biological programs. One of the best-studied examples of coactivator control of metabolic pathways is the peroxisome proliferator-activated receptor coactivator 1 (PGC-1) family. These proteins are strong activators of mitochondrial function and are thus dominant regulators of oxidative metabolism in a variety of tissues. The PGC-1 coactivators themselves are subject to powerful regulation at the transcriptional and posttranslational levels. Recent studies have elucidated the function of the PGC-1 coactivators in different tissues and have highlighted the implications of PGC-1 dysregulation in diseases such as diabetes, obesity, cardiomyopathy, or neurodegeneration.

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