Single-cell transcriptomics identifies ergothioneine as a mitochondrial protector to prevent AKI-to-CKD progression

This study investigates the role and mechanism of ergothioneine (EGT) in mitigating the progression of acute kidney injury (AKI) to chronic kidney disease (CKD). 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 demonstrate that EGT may significantly improve renal function parameters and attenuate renal injury and fibrosis. scRNA-seq analysis revealed that EGT may restore the expression of mitochondrial function-related genes in renal tubular epithelial cells, enhance oxidative phosphorylation and electron transport chain activity, thereby potentially promoting mitochondrial homeostasis. Furthermore, our in vitro experiments confirmed the protective effects of EGT on mitochondria in injured renal tubular epithelial cells, including reducing reactive oxygen species (ROS) generation, restoring diminished mitochondrial membrane potential, and increasing ATP production. These findings elucidate a mechanism by which EGT might delay AKI-to-CKD progression through multi-cellular coordination aimed at improving mitochondrial function, offering a promising therapeutic strategy for kidney diseases.