Activation of BNIP3-mediated mitophagy protects against renal ischemia-reperfusion injury

Chengyuan Tang, Hailong Han, Zhiwen Liu, Yuxue Liu, Lijun Yin, Juan Cai, Liyu He, Yu Liu, Guochun Chen, Zhuohua Zhang, Xiao-Ming Yin, Zheng Dong

Research output: Contribution to journalArticle

Abstract

Acute kidney injury (AKI) is a syndrome of abrupt loss of renal functions. The underlying pathological mechanisms of AKI remain largely unknown. BCL2-interacting protein 3 (BNIP3) has dual functions of regulating cell death and mitophagy, but its pathophysiological role in AKI remains unclear. Here, we demonstrated an increase of BNIP3 expression in cultured renal proximal tubular epithelial cells following oxygen-glucose deprivation-reperfusion (OGD-R) and in renal tubules after renal ischemia-reperfusion (IR)-induced injury in mice. Functionally, silencing Bnip3 by specific short hairpin RNAs in cultured renal tubular cells reduced OGD-R-induced mitophagy, and potentiated OGD-R-induced cell death. In vivo, Bnip3 knockout worsened renal IR injury, as manifested by more severe renal dysfunction and tissue injury. We further showed that Bnip3 knockout reduced mitophagy, which resulted in the accumulation of damaged mitochondria, increased production of reactive oxygen species, and enhanced cell death and inflammatory response in kidneys following renal IR. Taken together, these findings suggest that BNIP3-mediated mitophagy has a critical role in mitochondrial quality control and tubular cell survival during AKI.

Original languageEnglish (US)
Number of pages1
JournalCell death & disease
Volume10
Issue number9
DOIs
StatePublished - Sep 12 2019

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Proto-Oncogene Proteins c-bcl-2
Mitochondrial Degradation
Reperfusion Injury
Kidney
Acute Kidney Injury
Reperfusion
Cell Death
Oxygen
Glucose
Quality Control
Small Interfering RNA
Reactive Oxygen Species
Cell Survival
Mitochondria

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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Activation of BNIP3-mediated mitophagy protects against renal ischemia-reperfusion injury. / Tang, Chengyuan; Han, Hailong; Liu, Zhiwen; Liu, Yuxue; Yin, Lijun; Cai, Juan; He, Liyu; Liu, Yu; Chen, Guochun; Zhang, Zhuohua; Yin, Xiao-Ming; Dong, Zheng.

In: Cell death & disease, Vol. 10, No. 9, 12.09.2019.

Research output: Contribution to journalArticle

Tang, C, Han, H, Liu, Z, Liu, Y, Yin, L, Cai, J, He, L, Liu, Y, Chen, G, Zhang, Z, Yin, X-M & Dong, Z 2019, 'Activation of BNIP3-mediated mitophagy protects against renal ischemia-reperfusion injury', Cell death & disease, vol. 10, no. 9. https://doi.org/10.1038/s41419-019-1899-0
Tang, Chengyuan ; Han, Hailong ; Liu, Zhiwen ; Liu, Yuxue ; Yin, Lijun ; Cai, Juan ; He, Liyu ; Liu, Yu ; Chen, Guochun ; Zhang, Zhuohua ; Yin, Xiao-Ming ; Dong, Zheng. / Activation of BNIP3-mediated mitophagy protects against renal ischemia-reperfusion injury. In: Cell death & disease. 2019 ; Vol. 10, No. 9.
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