Mitochondrial Dysfunction-Evoked DHODH Acetylation is Involved in Renal Cell Ferroptosis during Cisplatin-Induced Acute Kidney Injury.

ABSTRACT: Several studies have observed renal cell ferroptosis during cisplatin-induced acute kidney injury (AKI). However, the mechanism is not completely clear. In this study, oxidized arachidonic acid (AA) metabolites are increased in cisplatin-treated HK-2 cells. Targeted metabolomics showed that the end product of pyrimidine biosynthesis is decreased and the initiating substrate of pyrimidine biosynthesis is increased in cisplatin-treated mouse kidneys. Mitochondrial DHODH, a key enzyme for pyrimidine synthesis, and its downstream product CoQH₂, are downregulated. DHODH overexpression attenuated but DHODH silence exacerbated cisplatin-induced CoQH₂ depletion and lipid peroxidation. Mechanistically, renal DHODH acetylation is elevated in cisplatin-exposed mice. Mitochondria

SUBMITTER: Liang NN 

PROVIDER: S-EPMC11578349 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature