The IDH1-R132H mutation aggravates cisplatin-induced acute kidney injury by promoting ferroptosis through disrupting NDUFA1 and FSP1 interaction.

ABSTRACT: The IDH1-R132H mutation is implicated in the development of various tumors. Whether cisplatin, a common chemotherapeutic agent, induces more significant renal toxicity in individuals with the IDH1-R132H mutation remains unclear. In this study, we observed that the IDH1-R132H mutation exacerbates mitochondrial lipid peroxidation and dysfunction in renal tubules, rendering the kidneys more susceptible to cisplatin-induced ferroptosis. The IDH1-R132H mutation increases methylation of the Ndufa1 promoter, thereby suppressing NDUFA1 transcription and translation. This suppression disrupts NDUFA1's interaction with FSP1, reducing its resistance to cisplatin-induced tubular epithelial cell death. As a consequence, ROS accumulates, lipid peroxidation occurs, and ferroptosis is triggered, thereby p

SUBMITTER: Lai K 

PROVIDER: S-EPMC11802792 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature