期刊
JOURNAL OF CELL SCIENCE
卷 122, 期 11, 页码 1906-1916出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.040188
关键词
Apoptosis; Bcl2; hexokinase; mitochondria; VDAC1
类别
资金
- Israel Science Foundation
- Israel Cancer Association
- Johnson and Johnson Corporate Office of Science and Technology
The release of mitochondrial-intermembrane-space proapoptotic proteins, such as cytochrome c, is a key step in initiating apoptosis. Our study addresses two major questions in apoptosis: how are mitochondrial pro-apoptotic proteins released and how is this process regulated? Accumulating evidence indicates that the voltage-dependent anion channel (VDAC) plays a central role in mitochondria-mediated apoptosis. Here, we demonstrate that the N-terminal domain of VDAC1 controls the release of cytochrome c, apoptosis and the regulation of apoptosis by anti-apoptotic proteins such as hexokinase and Bcl2. Cells expressing N-terminal truncated VDAC1 do not release cytochrome c and are resistant to apoptosis, induced by various stimuli. Employing a variety of experimental approaches, we show that hexokinase and Bcl2 confer protection against apoptosis through interaction with the VDAC1 N-terminal region. We also demonstrate that apoptosis induction is associated with VDAC oligomerization. These results show VDAC1 to be a component of the apoptosis machinery and offer new insight into the mechanism of cytochrome c release and how anti-apoptotic proteins regulate apoptosis and promote tumor cell survival.
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