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Using a cisplatin-induced mouse model of the AKI-to-CKD transition with EGT intervention, we combined histopathological examination, biochemical assays, and single-cell RNA sequencing (scRNA-seq) to provide evidence that EGT may improve renal function parameters and attenuate renal injury and fibrosis. scRNA-seq analysis revealed that EGT was associated with partial normalization of mitochondria-related gene expression in renal tubular epithelial cells, accompanied by enrichment of oxidative phosphorylation and electron transport chain pathways. Furthermore, our in vitro experiments supported a protective association of EGT with mitochondrial injury-related phenotypes in injured renal tubular epithelial cells, as indicated by reduced reactive oxygen species generation, partial preservation of mitochondrial membrane potential, and increased cellular ATP levels. These findings suggest that EGT may attenuate AKI-to-CKD progression in association with improved mitochondrial homeostasis, offering a potential therapeutic strategy for kidney diseases.<\/jats:p>","DOI":"10.1371\/journal.pone.0351630","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:35:25Z","timestamp":1782236125000},"page":"e0351630","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Single-cell transcriptomics identifies ergothioneine as a mitochondrial protector to prevent AKI-to-CKD 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