Overexpression of SIRT3 disrupts mitochondrial proteostasis and cell cycle progression

• Published in: Protein & cell 2016-04, Vol.7 (4), p.295-299
• Main Authors: Wang, Xiaofei, Tang, Haiping, Chen, Yuling, Chi, Binghuan, Wang, Shiyu, Lv, Yang, Wu, Di, Ge, Renshan, Deng, Haiteng
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Blotting, Western; Cell Biology; Cell Cycle Checkpoints; Cell Line, Tumor; Chaperonin 60 - metabolism; Developmental Biology; HEK293 Cells; Human Genetics; Humans; Letter; Life Sciences; Mitochondria - metabolism; Protein Science; Reactive Oxygen Species - metabolism; Real-Time Polymerase Chain Reaction; Sirtuin 3 - genetics; Sirtuin 3 - metabolism; Stem Cells; TCA循环; 人胚肾细胞; 线粒体蛋白; 细胞周期; 肿瘤发生; 肿瘤抑制基因; 过表达; 进程
• ISSN: 1674-800X; 1674-8018
• DOI: 10.1007/s13238-016-0251-z

Dear Editor, As a mitochondrial deacetylase, SIRT3 deacetylates many enzymes involved in central metabolism and maintains mitochondrial proteostasis （Verdin et al., 2010; Papa and Germain, 2014）. Substrates of SIRT3 include components of the respiratory complexes, proteins involved in fatty acid oxidation and TCA cycle （Yu et al., 2012）. SIRT3 activates MnSOD to maintain reactive oxygen species （ROS） home- ostasis and a loss of SIRT3 contributes to the age-associ- ated diseases （McDonnell et al., 2015; Qiu et al., 2010）. SIRT3 plays dual roles functioning as a tumor suppressor or a promoter in tumorigenesis and progression （Alhazzazi et al., 2011 ）. On one hand, SIRT3 regulates the cellular ROS level and maintains genomic stability, and mediates meta- bolic reprogramming to prevent tumorigenesis （Finley and Haigis, 2012）. As a result, the low expression of SIRT3 has been found in breast cancer, glioblastoma, colon cancer, osteosarcoma, prostate, and ovarian cancers （Kim et al., 2010; Finley and Haigis, 2012）. On the other hand, SIRT3 is a prosurvival factor that modulates p53 activities and is upregulated in oral cancer, the node-positive breast cancer, and bladder cancer （Ashraf et al., 2006; Alhazzazi et al., 2011）. These results suggest that SIRT3 possesses the tumor-type dependent function and its precise role needs to be elucidated in the context of a specific cancer. Clear cell renal cell carcinoma （ccRCC） is the most common histo- logical subtype of renal cancer （Cohen and McGovern, 2005）. The aims of the present study were to examine the expression of SIRT3 in ccRCC and to characterize effects of SIRT3 on tumorigenesis and progression using 293T human embryonic kidney cells as the model system that has cancer stem cell-like features （Debeb et al., 2010）.