Fig. 8

Graphical abstract illustrating MDHDH-induced GBM suppression. The reduced expression of MDHDH in GBM is attributed to EZH2-mediated epigenetic inhibition. MDHDH acts as a scaffold to promote binding of ubiquitin-modified MDH2 to PSMA1, triggering subsequent MDH2 degradation via the UPS. The degradation of MDH2 leads to the inefficacy of MAS, which is unable to maintain the essential NAD+/NADH ratio for substantial glycolysis. The abnormal metabolic state activates the AMPK/mTOR signaling pathway and induces autophagy to suppress GBM