Title |
Mito-priming as a method to engineer Bcl-2 addiction
|
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Published in |
Nature Communications, February 2016
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DOI | 10.1038/ncomms10538 |
Pubmed ID | |
Authors |
Jonathan Lopez, Margaux Bessou, Joel S. Riley, Evangelos Giampazolias, Franziska Todt, Tony Rochegüe, Andrew Oberst, Douglas R. Green, Frank Edlich, Gabriel Ichim, Stephen W. G. Tait |
Abstract |
Most apoptotic stimuli require mitochondrial outer membrane permeabilization (MOMP) in order to execute cell death. As such, MOMP is subject to tight control by Bcl-2 family proteins. We have developed a powerful new technique to investigate Bcl-2-mediated regulation of MOMP. This method, called mito-priming, uses co-expression of pro- and anti-apoptotic Bcl-2 proteins to engineer Bcl-2 addiction. On addition of Bcl-2 targeting BH3 mimetics, mito-primed cells undergo apoptosis in a rapid and synchronous manner. Using this method we have comprehensively surveyed the efficacy of BH3 mimetic compounds, identifying potent and specific MCL-1 inhibitors. Furthermore, by combining different pro- and anti-apoptotic Bcl-2 pairings together with CRISPR/Cas9-based genome editing, we find that tBID and PUMA can preferentially kill in a BAK-dependent manner. In summary, mito-priming represents a facile and robust means to trigger mitochondrial apoptosis. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 4 | 29% |
Australia | 1 | 7% |
Italy | 1 | 7% |
India | 1 | 7% |
United States | 1 | 7% |
Unknown | 6 | 43% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 9 | 64% |
Scientists | 3 | 21% |
Science communicators (journalists, bloggers, editors) | 2 | 14% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Japan | 1 | 1% |
Spain | 1 | 1% |
United States | 1 | 1% |
Italy | 1 | 1% |
Unknown | 77 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 18 | 22% |
Student > Ph. D. Student | 16 | 20% |
Student > Bachelor | 8 | 10% |
Student > Postgraduate | 6 | 7% |
Student > Master | 6 | 7% |
Other | 11 | 14% |
Unknown | 16 | 20% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 28 | 35% |
Agricultural and Biological Sciences | 14 | 17% |
Medicine and Dentistry | 6 | 7% |
Immunology and Microbiology | 6 | 7% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 5% |
Other | 7 | 9% |
Unknown | 16 | 20% |