Abstract
Mitochondrial outer membrane permeabilization (MOMP) is considered the ‘point of no return’ as this event is responsible for engaging the apoptotic cascade in numerous cell death pathways. MOMP is directly governed by a subset of the BCL-2 family of proapoptotic proteins, which induce disruptions in the outer mitochondrial membrane (OMM) and subsequent release of death-promoting proteins like cytochrome c. The proposal here is centered on our hypothesis that MOMP is dictated by an interaction between the cytosol and the OMM, and although proteins of the OMM may be important in the process, the ‘decision’ to undergo apoptosis originates within the cytosol with no participation (in terms of yes, no and when) by mitochondria.
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Abbreviations
- APAF-1:
-
apoptotic protease-activating factor-1
- CICD:
-
caspase-independent cell death
- DRP-1:
-
dynamin-related protein 1
- IMM:
-
inner mitochondrial membrane
- MOMP:
-
mitochondrial outer membrane permeabilization
- mPT:
-
mitochondrial permeability transition
- OMM:
-
outer mitochondrial membrane
- OXPHOS:
-
oxidative phosphorylation
- PBR:
-
peripheral benzodiazepine receptor
- ROS:
-
reactive oxygen species
- VDAC:
-
voltage-dependent anion channel
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Acknowledgements
Our work is the poorer for the loss of our dear and valuable colleague, Stan Korsmeyer, whose leadership in this field is without compare. This review celebrates his accomplishments, and how his insights and discoveries have impacted on our thinking, research and understanding of the function of the BCL-2 family in apoptosis. We are dedicated to pursuing the work that he inaugurated, and in doing so, hope in our small way to keep his wonderful scientific spirit vibrant. This is for Stan. We only fervently wish we could discuss these ideas with him.
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Chipuk, J., Bouchier-Hayes, L. & Green, D. Mitochondrial outer membrane permeabilization during apoptosis: the innocent bystander scenario. Cell Death Differ 13, 1396–1402 (2006). https://doi.org/10.1038/sj.cdd.4401963
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DOI: https://doi.org/10.1038/sj.cdd.4401963
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