Fig. 1

Proposed mechanism of MARCHF6 monitoring the levels of intracellular NADPH and regulating cell ferroptosis. When the intracellular levels of NADPH are high, the NADPH will directly bind with MarA, and interaction with RING thereby preventing the interaction between MarI and MarA, results in increasing the ubiquitin ligase activity of MARCHF6, promoting the ubiquitin-dependent rapid degradation of p53 and ACSL4, increasing the expression of GPX4 and SLC7A11 and decreasing the lipid peroxidation, resulting in anti-ferroptosis. When the intracellular levels of NADPH are low, the MarI binds with MarA thereby blocking the interaction of RING with MarA. This results in reducing the ubiquitin ligase activity of MARCHF6, blocking the ubiquitin-dependent degradation of p53 and ACSL4, inhibiting the expression of GPX4 and SLC7A11 and increasing the lipid peroxidation, resulting in ferroptosis