Myostatin induces mitochondrial metabolic alteration and typical apoptosis in cancer cells

被引：33
作者：
Liu, Y. [1 ,2 ]
Cheng, H. [3 ,4 ]
Zhou, Y. [3 ,4 ]
Zhu, Y. [5 ]
Bian, R. [3 ,4 ]
Chen, Y. [3 ,4 ]
Li, C. [3 ,4 ]
Ma, Q. [1 ,2 ]
Zheng, Q. [1 ,2 ]
Zhang, Y. [2 ,3 ,4 ]
Jin, H. [1 ]
Wang, X. [1 ]
Chen, Q. [1 ,5 ]
Zhu, D. [2 ,3 ,4 ]
机构：
[1] Chinese Acad Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing, Peoples R China
[2] Chinese Acad Sci, Grad Sch, Beijing, Peoples R China
[3] Chinese Acad Med Sci, Inst Basic Sci, Natl Lab Med Mol Biol, Beijing 100005, Peoples R China
[4] Peking Union Med Coll, Sch Basic Med, Beijing 100021, Peoples R China
[5] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China
来源：
CELL DEATH & DISEASE | 2013年 / 4卷
基金：
中国国家自然科学基金;
关键词：
myostatin; apoptosis; VDAC1/HKII; mitochondrial metabolism;
D O I：
10.1038/cddis.2013.31
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Myostatin, a member of the transforming growth factor-beta superfamily, regulates the glucose metabolism of muscle cells, while dysregulated myostatin activity is associated with a number of metabolic disorders, including muscle cachexia, obesity and type II diabetes. We observed that myostatin induced significant mitochondrial metabolic alterations and prolonged exposure of myostatin induced mitochondria-dependent apoptosis in cancer cells addicted to glycolysis. To address the underlying mechanism, we found that the protein levels of Hexokinase II (HKII) and voltage-dependent anion channel 1 (VDAC1), two key regulators of glucose metabolisms as well as metabolic stress-induced apoptosis, were negatively correlated. In particular, VDAC1 was dramatically upregulated in cells that are sensitive to myostatin treatment whereas HKII was downregulated and dissociated from mitochondria. Myostatin promoted the translocation of Bax from cytosol to mitochondria, and knockdown of VDAC1 inhibited myostatin-induced Bax translocation and apoptosis. These apoptotic changes can be partially rescued by repletion of ATP, or by ectopic expression of HKII, suggesting that perturbation of mitochondrial metabolism is causally linked with subsequent apoptosis. Our findings reveal novel function of myostatin in regulating mitochondrial metabolism and apoptosis in cancer cells. Cell Death and Disease (2013) 4, e494; doi:10.1038/cddis.2013.31; published online 14 February 2013
引用
收藏
页码：e494 / e494
页数：11
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