(K) A schematic diagram depicting the regulation of lipogenesis by PKM2. ER located PKM2 inhibits VCP activity, which is essential for NRF1 precursor cleavage. Cleaved NRF1 acts as a transcriptional factor for TMEM33. ER localized TMEM33 inhibits SREBPs activity through promoting SCAP degradation in RNF5-dependent manner. Knocking out PKM2 leads to increased NRF1 cleavage and TMEM33 expression. Consequentially, SCAP is destabilized by RNF5-mediated ubiquitination and expression levels of lipid synthetic genes are decreased. 