The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1

Li Xiao, Xiaoxuan Xu, Fan Zhang, Ming Wang, Yan Xu, Dan Tang, Jiahui Wang, Yan Qin, Yu Liu, Chengyuan Tang, Liyu He, Anna Greka, Zhiguang Zhou, Fuyou Liu, Zheng Dong, Lin Sun

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Mitochondria play a crucial role in tubular injury in diabetic kidney disease (DKD). MitoQ is a mitochondria-targeted antioxidant that exerts protective effects in diabetic mice, but the mechanism underlying these effects is not clear. We demonstrated that mitochondrial abnormalities, such as defective mitophagy, mitochondrial reactive oxygen species (ROS) overexpression and mitochondrial fragmentation, occurred in the tubular cells of db/db mice, accompanied by reduced PINK and Parkin expression and increased apoptosis. These changes were partially reversed following an intraperitoneal injection of mitoQ. High glucose (HG) also induces deficient mitophagy, mitochondrial dysfunction and apoptosis in HK-2 cells, changes that were reversed by mitoQ. Moreover, mitoQ restored the expression, activity and translocation of HG-induced NF-E2-related factor 2 (Nrf2) and inhibited the expression of Kelch-like ECH-associated protein (Keap1), as well as the interaction between Nrf2 and Keap1. The reduced PINK and Parkin expression noted in HK-2 cells subjected to HG exposure was partially restored by mitoQ. This effect was abolished by Nrf2 siRNA and augmented by Keap1 siRNA. Transfection with Nrf2 siRNA or PINK siRNA in HK-2 cells exposed to HG conditions partially blocked the effects of mitoQ on mitophagy and tubular damage. These results suggest that mitoQ exerts beneficial effects on tubular injury in DKD via mitophagy and that mitochondrial quality control is mediated by Nrf2/PINK.

Original languageEnglish (US)
Pages (from-to)297-311
Number of pages15
JournalRedox Biology
Volume11
DOIs
StatePublished - Apr 1 2017

Keywords

  • Diabetic kidney disease
  • Mitophagy
  • Mitoq
  • Tubular

ASJC Scopus subject areas

  • Organic Chemistry
  • Clinical Biochemistry

Fingerprint Dive into the research topics of 'The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1'. Together they form a unique fingerprint.

  • Cite this

    Xiao, L., Xu, X., Zhang, F., Wang, M., Xu, Y., Tang, D., Wang, J., Qin, Y., Liu, Y., Tang, C., He, L., Greka, A., Zhou, Z., Liu, F., Dong, Z., & Sun, L. (2017). The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1. Redox Biology, 11, 297-311. https://doi.org/10.1016/j.redox.2016.12.022