Fig. 6

Schematic illustration of NADPH-mediated autoregulation mechanism for adaptation to oxidative stress in A. nidulans. A–C Under normal conditions (A, Homeostasis stage) the NADPH pool provides an adequate supply of NADPH to reduce AnCF to its activated state, which will suppress NapA and subsequently lower the levels of PrxA. Due to the absence of high consumption of NADPH, the intracellular NADPH pool is maintained at a high level causing G6PD activity inhibition. Thus, the inflow of NADPH from G6PD to the NADPH pool is quite limited. Once fungi encounter H₂O₂ (B, Adaptive response stage), NADPH is suddenly needed to decompose H₂O₂ using PrxA, leading to an immediate drop within 30 min. Inevitably, the inflow of NADPH from the NADPH pool to reduce AnCF is declined. The accumulation of oxidized AnCF activates napA to supply more PrxA until the PrxA pool is saturated, accelerating NADPH consumption while resisting H₂O₂. Next, the depletion of NADPH reactivates G6PD, and NADPH eventually reaches to the initial level in the next 30 min (C, Cell survival stage). The increased NADPH level triggers the reactivation of AnCF, which consequently shuts down NapA induction, represses NapA activity via NADPH-dependent reduction to block PrxA induction, and ultimately keeps the PrxA pool at a moderate level (C, Cell survival stage)