Sirt3-mediated mitophagy protects tumor cells against apoptosis under hypoxia

Aimin Qiao, Kuansong Wang, Yunsheng Yuan, Yidi Guan, Xingcong Ren, Lanya Li, Xisha Chen, Feng Li, Alex F. Chen, Jianda Zhou, Jin Ming Yang, Yan Cheng

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Sirt3, a mitochondrial deacetylase, participates in the regulation of multiple cellular processes through its effect on protein acetylation. The objective of this study was to explore the role of Sirt3 in the mitochondrial autophagy (mitophagy), a process of the specific autophagic elimination of damaged mitochondria. We found that silencing of Sirt3 expression in human glioma cells by RNA interference blunted the hypoxia-induced the localization of LC3 on the mitochondria, and the degradation of mitochondria. These results suggest an important involvement of this protein deacetylase in the induction of mitophagy in cancer cells subjected to hypoxia. Further, we demonstrated that Sirt3 activated the hypoxia-induced mitophagy by increasing the interaction of VDAC1 with Parkin. In the cells subjected to hypoxia, inhibition of Sirt3-mediated mitophagy further decreased the mitochondrial membrane potential, and increased the accumulation of ROS that triggers the degradation of anti-apoptotic proteins Mcl-1 and survivin through the proteasomal pathway. Silencing of Sirt3 expression also promoted apoptosis, and enhanced the sensitivity of cancer cells to hypoxia. The regulatory role of Sirt3 in autophagy and apoptosis was also observed in human breast cancer cells. The results of the current study reveal Sirt3 as a novel regulator coupling mitophagy and apoptosis, two important cellular processes that determine cellular survival and death.

Original languageEnglish (US)
Pages (from-to)43390-43400
Number of pages11
JournalOncotarget
Volume7
Issue number28
DOIs
StatePublished - Jan 1 2016

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All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Qiao, A., Wang, K., Yuan, Y., Guan, Y., Ren, X., Li, L., Chen, X., Li, F., Chen, A. F., Zhou, J., Yang, J. M., & Cheng, Y. (2016). Sirt3-mediated mitophagy protects tumor cells against apoptosis under hypoxia. Oncotarget, 7(28), 43390-43400. https://doi.org/10.18632/oncotarget.9717