Underexpression of the transcriptional coactivator PGC-1α is causally linked to certain neurodegenerative disorders, including Huntington's Disease (HD). HD pathoprogression is also associated with aberrant NMDAR activity, in particular an imbalance between synaptic versus extrasynaptic (NMDAR(EX)) activity. Here we show that PGC-1α controls NMDAR(EX) activity in neurons and that its suppressio...

The β3-adrenergic receptor (AR) signaling pathway is a major component of adaptive thermogenesis in brown and white adipose tissue during cold acclimation. The β3-AR signaling highly induces the expression of transcriptional coactivator PGC-1α and its splice variant N-terminal (NT)-PGC-1α, which in turn activate the transcription program of adaptive thermogenesis by co-activating a number of tr...

Human peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) is a key coactivator in the regulation of gene transcriptional activity in normal tissues. However, it is not clear whether it is involved in the angiogenesis and metabolism of multiple myeloma (MM). The aim of the present study was to investigate the role of PGC-1α in MM. Small interfering RNA (siRNA) was used to inhibi...

Alterations in the expression and activity of the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1α (ppargc1a or PGC-1α) have been reported in multiple movement disorders, yet it is unclear how a lack of PGC-1α impacts transcription and function of the cerebellum, a region with high PGC-1α expression. We show here that mice lacking PGC-1α exhibit ataxia in ...

The peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1) proteins are key regulators of cellular bioenergetics and are accordingly expressed in tissues with a high energetic demand. For example, PGC-1α and PGC-1β control organ function of brown adipose tissue, heart, brain, liver and skeletal muscle. Surprisingly, despite their prominent role in the control of mitochondrial biogen...

AngII (angiotensin II)-induced excessive ROS (reactive oxygen species) generation and proliferation of VSMCs (vascular smooth muscle cells) is a critical contributor to the pathogenesis of atherosclerosis. PGC-1α [PPARγ (peroxisome-proliferator-activated receptor γ) co-activator-1α] is involved in the regulation of ROS generation, VSMC proliferation and energy metabolism. The aim of the present...

The transcriptional coactivator PPARγ coactivator-1α (PGC-1α) is a critical regulator of mitochondrial content and function in skeletal muscle. PGC-1α may also mediate mitochondrial adaptations in response to chronic contractile activity (CCA). To characterize the essential role of PGC-1α in organelle biogenesis, C₂C₁₂ murine myotubes were transfected with PGC-1α-specific siRNA and subjected to...

OBJECTIVE Food intake and whole-body energy homeostasis are controlled by agouti-related protein (AgRP) and pro-opiomelanocortin (POMC) neurons located in the arcuate nucleus of the hypothalamus. Key energy sensors, such as the AMP-activated protein kinase (AMPK) or sirtuin 1 (SIRT1), are essential in AgRP and POMC cells to ensure proper energy balance. In peripheral tissues, the transcriptiona...