期刊
MOLECULAR CELL
卷 57, 期 5, 页码 860-872出版社
CELL PRESS
DOI: 10.1016/j.molcel.2015.01.018
关键词
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资金
- Royal Society, an EU
- BBSRC [BB/K008374/1]
- European Union
- Science Foundation Ireland [09-RFP-BIC2375]
- EMBO [ALTF 55-2013]
- l'Association pour la recherche sur le cancer (ARC)
- Cancer Research UK
- Science Foundation Ireland (SFI) [09/RFP/BIC2375] Funding Source: Science Foundation Ireland (SFI)
- Biotechnology and Biological Sciences Research Council [BB/K008374/1] Funding Source: researchfish
- Cancer Research UK [22311] Funding Source: researchfish
- Medical Research Council [G0802755] Funding Source: researchfish
- BBSRC [BB/K008374/1] Funding Source: UKRI
- MRC [G0802755] Funding Source: UKRI
During apoptosis, the mitochondrial outer membrane is permeabilized, leading to the release of cytochrome c that activates downstream caspases. Mitochondrial outer membrane permeabilization (MOMP) has historically been thought to occur synchronously and completely throughout a cell, leading to rapid caspase activation and apoptosis. Using a new imaging approach, we demonstrate that MOMP is not an all-or-nothing event. Rather, we find that a minority of mitochondria can undergo MOMP in a stress-regulated manner, a phenomenon we term minority MOMP.'' Crucially, minority MOMP leads to limited caspase activation, which is insufficient to trigger cell death. Instead, this caspase activity leads to DNA damage that, in turn, promotes genomic instability, cellular transformation, and tumorigenesis. Our data demonstrate that, in contrast to its well-established tumor suppressor function, apoptosis also has oncogenic potential that is regulated by the extent of MOMP. These findings have important implications for oncogenesis following either physiological or therapeutic engagement of apoptosis.
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