Drp1-dependent mitophagy protects against cisplatin-induced apoptosis of renal
tubular epithelial cells by improving mitochondrial function
#MMPMID28423497
Zhao C
; Chen Z
; Qi J
; Duan S
; Huang Z
; Zhang C
; Wu L
; Zeng M
; Zhang B
; Wang N
; Mao H
; Zhang A
; Xing C
; Yuan Y
Oncotarget
2017[Mar]; 8
(13
): 20988-21000
PMID28423497
show ga
Cisplatin chemotherapy often causes acute kidney injury (AKI) in cancer patients.
There is increasing evidence that mitochondrial dysfunction plays an important
role in cisplatin-induced nephrotoxicity. Degradation of damaged mitochondria is
carried out by mitophagy. Although mitophagy is considered of particular
importance in protecting against AKI, little is known of the precise role of
mitophagy and its molecular mechanisms during cisplatin-induced nephrotoxicity.
Also, evidence that activation of mitophagy improved mitochondrial function is
lacking. Furthermore, several evidences have shown that mitochondrial fission
coordinates with mitophagy. The aim of this study was to investigate whether
activation of mitophagy protects against mitochondrial dysfunction and renal
proximal tubular cells injury during cisplatin treatment. The effect of
mitochondrial fission on mitophagy was also investigated. In cultured human renal
proximal tubular cells, we observed that 3-methyladenine, a pharmacological
inhibitor of autophagy, blocked mitophagy and exacerbated cisplatin-induced
mitochondrial dysfunction and cells injury. In contrast, autophagy activator
rapamycin enhanced mitophagy and protected against the harmful effects of
cisplatin on mitochondrial function and cells viability. Suppression of
mitochondrial fission by knockdown of its main regulator dynamin-related
protein-1 (Drp1) decreased cisplatin-induced mitophagy. Meanwhile, Drp1
suppression protected against cisplatin-induced cells injury by inhibiting
mitochondrial dysfunction. Our results provide evidence that Drp1-depedent
mitophagy has potential as renoprotective targets for the treatment of
cisplatin-induced AKI.
|Acute Kidney Injury/metabolism/pathology/*prevention & control
[MESH]
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