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Mechanistically, PHGDH deficiency suppresses cytoplasmic glutathione (GSH) synthesis but enhances mitochondrial reactive oxygen species (mtROS), which triggers hypoxia-inducible factor–1α (HIF-1α) signaling to regulate nuclear specificity protein 1 (SP1) and nuclear respiratory factor 1 (NRF1) expression, resulting in increased mitochondrial biogenesis
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