Cell Stress and Chaperones

, Volume 24, Issue 2, pp 369–383 | Cite as

Sirtuin 3 inhibition induces mitochondrial stress in tongue cancer by targeting mitochondrial fission and the JNK-Fis1 biological axis

  • Jichi Zhou
  • Menghan Shi
  • Man Li
  • Long Cheng
  • Jinsuo Yang
  • Xin HuangEmail author
Original Paper


Sirtuin 3 (Sirt3)-modified mitochondrial fission participates in the progression of several types of cancers. However, its role in tongue cancer requires investigation. The aim of our study is to determine whether Sirt3 knockdown regulates the viability of tongue cancer cells via modulating mitochondrial fission. Two types of tongue cancer cells were used in the present study, and siRNA was transfected into the cells to suppress Sirt3 expression. Mitochondrial function and cell apoptosis were determined via immunofluorescence, Western blotting, ELISA, and qPCR assays. A pathway blocker was applied to verify the role of the JNK-Fis1 signaling pathway in regulation of mitochondrial fission. The present study showed that loss of Sirt3 promoted tongue cancer cell death in a manner dependent on mitochondrial apoptosis. Mitochondrial oxidative stress, energy metabolism disorder, mitochondrial cyt-c liberation, and mitochondrial apoptosis activation were observed after Sirt3 silencing. Furthermore, we demonstrated that Sirt3 knockdown activated mitochondrial stress via triggering Fis1-related mitochondrial fission and that inhibition of Fis1-related mitochondrial fission abrogated the pro-apoptotic effect of Sirt3 knockdown on tongue cancer cells. To this end, we found that Sirt3 modulated Fis1 expression via the c-Jun N-terminal kinases (JNK) signaling pathway and that blockade of the JNK pathway attenuated mitochondrial stress and repressed apoptosis in Sirt3 knockdown cells. Altogether, our results identified a tumor-suppressive role for Sirt3 deficiency in tongue cancer via activation of the JNK-Fis1 axis and subsequent initiation of fatal mitochondrial fission. Given these findings, strategies to repress Sirt3 activity and enhance the JNK-Fis1-mitochondrial fission cascade have clinical benefits for patients with tongue cancer.


Tongue cancer Mitochondrial fission Sirt3 JNK-Fis1 signaling pathway Mitochondrial dysfunction 



This research was supported by the Scientific Research Common Program of Beijing Municipal Commission of Education (KM201710025020).

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests.


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Copyright information

© Cell Stress Society International 2019

Authors and Affiliations

  • Jichi Zhou
    • 1
  • Menghan Shi
    • 1
  • Man Li
    • 1
  • Long Cheng
    • 1
  • Jinsuo Yang
    • 1
  • Xin Huang
    • 1
    Email author
  1. 1.Department of Oral and Maxillofacial Surgery, Beijing Stomatological HospitalCapital Medical UniversityBeijingChina

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