What is PGC 1a activated by?
During fasting, the expression of PGC-1α is activated by glucagon and catecholamines via the stimulation of the cAMP pathway and the CREB transcription factor. PGC-1α then coactivates a variety of transcription factors such as hepatic nuclear factor-4α, glucocorticoid receptor, and forkhead box O1 (FOXO1).
Is PGC 1α a protein?
PGC-1α expression is tightly regulated, it is a highly labile protein, and it interacts with various proteins—the known attributes of intrinsically disordered proteins (IDPs).
What is pgc1a?
PGC-1alpha stimulates mitochondrial biogenesis and promotes the remodeling of muscle tissue to a fiber-type composition that is metabolically more oxidative and less glycolytic in nature, and it participates in the regulation of both carbohydrate and lipid metabolism.
What is mitochondrial biogenesis and why is it a good thing?
Mitochondrial biogenesis helps the cell to renew the mitochondrial network and, consequently, to improve mitochondrial function, slowing down the cascade of damage caused by mitochondrial dysfunction (one of the nine hallmarks of aging).
What increases mitochondrial biogenesis?
Mitochondrial biogenesis is increased, among other factors, by endurance exercise and caloric restriction. Understanding the molecular mechanisms regulating mitochondrial biogenesis may provide important therapeutic targets to prevent and treat numerous diseases, such as Type 2 diabetes.
What is mitochondrial capacity?
The maximal rate of free energy production from aerobic metabolism of glycogen was calculated from the mitochondrial activities and estimates of the DeltaG or ATP hydrolysis and the efficiency of the actin-myosin reaction.
What is the sirt1/ampk cycle?
The hypothetical SIRT1/AMPK cycle and its significance. A decrease in energy state or activation of AMPK by other means leads to activation of SIRT1, perhaps by increasing NAD + or the NAD/NADH ratio ( 8) and/or the activity of Nampt ( 23 ). SIRT1 then deacetylates and activates LKB1, which in turn activates AMPK.
How is SirT1 involved in kidney cancer?
Through TCGA database, it was revealed that among the numerous downstream signals of SIRT1, AMPK expression was closely associated with SIRT1 expression in kidney cancer (48). SIRT1 activation leads to deacetylation of lysine residues on liver kinase B1 (LKB1), which in turn enhances LKB1 kinase activity and leads to AMPK phosphorylation (49).
What is the role of AMPK in kidney cancer?
AMPK is an enzyme closely associated with cell energy metabolism, and as a downstream molecule of SIRT1, it has a strong association with it in kidney cancer (53). Western blotting and immunofluorescence were used in the present study to confirm that when regulating SIRT1 expression, the levels of phosphorylated AMPK also changed in the same way.
Do AMP-activated protein kinases affect PGC-1alpha activity?
Recent findings: Two metabolic sensors, AMP-activated protein kinase (AMPK) and SIRT1 have been described to directly affect PGC-1alpha activity through phosphorylation and deacetylation, respectively.