EGFR and non-small cell lung carcinoma: Proline synthesis mediated by Δ1-pyrroline-5-carboxylate (P5C) reductases (PYCRs) and proline degradation through PRODH constitute a “proline cycle” between the cytosol and mitochondria.88 In EGFR-mutated non-small-cell lung cancer, constitutive downstream activation of the PI3K pathway drives proline synthesis, which fuels EGFR-regulated proline oxidation.161 The activity of PRODH decreases the efficiency of mitochondrial electron transport, driving the production of ROS from the QO site of complex III through Mechanism B.