Excess ammonia is produced during fasting when amino acids are used for glucogenesis. Together with ureagenesis, glucogenesis occurs in periportal hepatocytes mediated mainly through the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). In vivo experiments showed that fasting strongly stimulated mice glucagon secretion, hepatic PGC-1α, sirtuin 3 (SIRT3) and sirtuin ...

Following acute myocardial infarction (MI), cardiomyocyte survival depends on its mitochondrial oxidative capacity. Cell death is normally followed by activation of the immune system. Peroxisome proliferator activated receptor γ-coactivator 1α (PGC-1α) is a transcriptional coactivator and a master regulator of cardiac oxidative metabolism. PGC-1α is induced by hypoxia and facilitates the recove...

Peroxisome proliferator-activated receptor γ (PPARγ) is part of a nuclear receptor superfamily that regulates gene expression involved in cell differentiation, proliferation, immune/inflammation response, and lipid metabolism. PPARγ coactivator-1α (PGC-1α), initially identified as a PPARγ-interacting protein, is an important regulator of diverse metabolic pathways, such as oxidative metabolism ...

Growing evidence has shown that podocyte number is a critical determinant for the development of glomerulosclerosis and progressive renal failure. We previously reported that mitochondrial dysfunction (MtD) is an early event in podocyte injury. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is an important modulator of mitochondrial biogenesis. Here, we investigated the ro...

The age-related impairment in muscle function results in a drastic decline in motor coordination and mobility in elderly individuals. Regular physical activity is the only efficient intervention to prevent and treat this age-associated degeneration. However, the mechanisms that underlie the therapeutic effect of exercise in this context remain unclear. We assessed whether endurance exercise tra...

Recent evidence suggests that reactive oxygen species (ROS) produced by inflammatory cells drive axonal degeneration in active multiple sclerosis (MS) lesions by inducing mitochondrial dysfunction. Mitochondria are endowed with a variety of antioxidant enzymes, including peroxiredoxin-3 and thioredoxin-2, which are involved in limiting ROS-induced damage. In this study, we explored the distribu...

BACKGROUND Mitochondrial function is dramatically altered in heart failure (HF). This is associated with a decrease in the expression of the transcriptional coactivator PGC-1α, which plays a key role in the coordination of energy metabolism. Identification of compounds able to activate PGC-1α transcription could be of future therapeutic significance. METHODOLOGY/PRINCIPAL FINDINGS We thus dev...

The coactivator PGC-1α is a key regulator of mitochondrial biogenesis and respiration, mediating expression of several transcription factors required for these programs. Three new studies reveal that PGC-1α expression is downregulated in patients with Huntington’s disease (HD) and in several animal models of this neurodegenerative disorder, implicating PGC-1α in HD pathogenesis and providing a ...

PGC-1α is a transcription coactivator centrally involved in the regulation of energy balance and metabolism. A recent study in Cell Metabolism adds another role for Pgc-1α, namely gene regulation in mitochondrial maintenance and metabolic homeostasis. The latest findings indicate significant increases in levels of DNA methylation within the promoter region of the Pgc-1α gene within human skelet...