Auszug aus einer interessanten Artikelreihe von James Watson:
There is strong evidence now that the levels of PGC-1a in cells is regulated primarily by the degradation rate of PGC-1a, and only secondarily by the gene expression of the PGC-1a gene. There are two degradation pathways for PGC-1a. The two pathways are the Ubiquitin Proteasome system (UPS) and the ubiquitin-independent proteasome system called 20S PC..
Under conditions of no oxidative stress, the UPS system may regulate PGC-1a levels within the cell. However when the cell is under cellular stress and the PGC-1a protein is damaged by ROS-induced oxidation, the 20S proteasome controls the degradation rate of PGC-1a. NQO1 is the “gate-keeper” for this 20S PC system that prevents PGC-1a from being degraded during periods of cellular oxidative stress. Thus with aging, the 20S PC system is more important than the26S proteasome (i.e. the UPS) and thus the 20S proteasome degrades PGC-1a in the cell, unless NQO1 protects it from degradation. Thus it appears that under conditions of oxidative stress, such as with aging, NQO1 may be a major factor that controls the concentration of PGC-1a in the cell.
This is why I was shocked to find out that NQO1 actually regulates PGC-1a, not by the increase in expression of the NQO1 gene, but the the rate that PGC-1a is degraded. Expression of NQ01 keeps PGC-1a from being degraded. What I found out is that the level of PGC-1a protein in a cell is primarily determined by its degradation rate, not its synthesis rate.
Fazit: für einen möglichst hohen Spiegel an PGC-1a ist weniger die Expression dieses Proteins hochzufahren als vielmehr die Abbaurate zu modulieren. Wie, wird in der Artikelreihe angerissen. NQO1 etwa macht dies und erhöht ebenso die NAD/NADH-Ratio? Wie macht man dies? Zum Beispiel mit Beta-Lapachin (günstig: Lapacho-Tee!) und Quercetin.