Mitophagy and oxidative stress in chronic kidney disease (Review)

Chronic kidney disease (CKD) progression is driven by a harmful interplay between impaired mitophagy and sustained oxidative stress. Under normal conditions, mitophagy serves as a protective mechanism by removing damaged mitochondria and limiting the production of reactive oxygen species. However, in CKD, a self‑reinforcing cycle of mitochondrial dysfunction, defective mitophagy oxidative stress, and inflammation occurs, which promotes fibrosis. The present review examines the molecular mechanisms governing mitophagy, with a specific focus on the regulatory roles of core signaling pathways, namely the PTEN‑induced kinase l/Parkin, BCL2 interacting protein 3/Nip3‑like protein X and FUN14 domain‑containing protein l pathways, and how their disruption contributes to CKD. The mechanistic crosstalk between mitophagy and oxidative stress is highlighted as a central pathogenic axis in CKD progression. In addition, emerging therapeutic strategies that aim to restore mitophagy and enhance antioxidant capacity are discussed, suggesting new strategies for targeted CKD treatment.