Fig. 7: Model of oxygen-dependent regulation of cholesterol biosynthesis.
From: A HIF independent oxygen-sensitive pathway for controlling cholesterol synthesis
Schematic of the oxygen-dependent regulation of SREBP2. In 21% oxygen and sterol replete conditions, SREBP2 is held in the ER through its interaction with SCAP/INSIGs, and basal SREBP2 turnover by MARCHF6 is low (top left). Sterol depletion releases SREBP2 from SCAP/INSIGs, and SREBP2 undergoes processing in the Golgi to generate the N-SRE transcription factor (bottom left). In hypoxia, NAPDH accumulates, increasing MARCHF6 activity in a proportional manner to oxygen availability (top right). This promotes SREBP2 degradation in the ER, and this shuts down cholesterol synthesis in sterol deplete conditions (bottom right).
