Fig. 7: Model describing the role of mitochondria in maintaining NADPH homeostasis.

Proposed model showing how mitochondrial-derived malate in intact cells, can sustain NADPH levels in the absence of optimal PPP activity. Conversely, cells with severe impairments in the ETC redirect pyruvate and/or glutamine through non-canonical TCA cycle as sources to generate malate. Under these conditions, ETC-deficient cells heavily rely on ME1 expression to maintain NADPH levels and ensure cellular fitness. This figure was created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license.