PINK1/Parkin-mediated mitophagy is activated in cisplatin nephrotoxicity to protect against kidney injury

Abstract

Cisplatin is a widely used chemotherapeutic drug with notorious toxicity in the kidneys, which involves mitochondrial dysfunction and damage in renal tubular cells. Mitophagy is a form of selective autophagy that removes damaged or dysfunctional mitochondria to maintain cellular homeostasis. In this study, we have used mouse and cell models to examine the role and regulation of mitophagy in cisplatin nephrotoxicity. Cisplatin treatment was associated with the activation of autophagy and mitophagy. Rapamycin, a pharmacological inhibitor of mTOR, stimulated autophagy and mitophagy, and alleviated the development of cisplatin nephrotoxicity. PINK1 and Parkin were increased in kidney tissues during cisplatin treatment of mice. In PINK1 or Parkin gene knockout mouse models, both basal and cisplatin-induced mitophagy in kidneys were defective. Compared with wild-type littermates, PINK1 and Parkin knockout mice showed more severe renal functional loss, tissue damage, and apoptosis during cisplatin treatment. The results suggest that PINK1/Parkin-mediated mitophagy is activated in cisplatin nephrotoxicity and has a protective role against kidney injury.

Mitophagy-dependent macrophage reprogramming protects against kidney fibrosis

“…Mitophagy is found to be induced during acute kidney injury (14,22,37,38) and compromised during CKD in animal models (39,40). Mitochondrial dysfunction is also reported in human kidney disease (33).…”

P53 and Parkin co-regulate mitophagy in bone marrow mesenchymal stem cells to promote the repair of early steroid-induced osteonecrosis of the femoral head

“…Some studies have shown that P53 can interact with Parkin's RING0 region 30,31 . The PINK1-Parkin pathway is the most important pathway by which mitophagy is mediated 42 ; therefore, to further study whether P53 regulated mitophagy via this pathway, we continued to treat BMSCs for 24 h using an H 2 O 2 (1000 μM)-simulated OS. − Parkin groups.…”

Alteration of Drp1 Expression in Drosophila Models of Parkinson Disease

“…The loss of the park protein is a cause of great cellular stress as a major mitophagy mechanism is compromised to potentially result in the accumulation of non-functional mitochondria. Under normal circumstances, the park ubiquitin ligase recruits the Drp1 protein to mediate mitochondrial fragmentation during mitophagy [20,49]. In mouse embryonic broblasts, loss of park does not have any effect upon the number of mitochondria [50].…”