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TS inhibition by 5FU regulates mitochondrial biogenesis through mTORPGC1 signalling 5FU has a multimodal mechanism of action: promoting DNA damage directly via its metabolite FdUTP or by inhibition of TS via FdUMP, depleting the pool of thymidine available for DNA synthesis, and causing RNA damage via FUTP (Fig

Corroborating these findings, immunoblot analysis of whole-kidney lysates demonstrated that UUO-induced upregulation of fibrotic (CCN2, FN1, COL1A1, and COL3A1) and ferroptotic (HMOX1) markers, alongside downregulation of GPX4, was more prominent in WT mice relative to KO littermates (Fig

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