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nature portfolio permissions reprints privacy policy nature mitochondrial permeability transition advertising programmed cell death social media plays bi-functional roles cell death differ personal data data protection permissions cell-free systems cell death article kroemer breast cancer cells privacy mitochondrial function constitutes explore content similar content journals search log european economic area obligatory early event molecular mechanism accounting trigger nuclear manifestations rate-limiting event highly bioactive molecule signal substance 6-formylindolo[3 bax genes associate tmbim protein family accepting optional cookies ancestral unicellular eukaryotes bcl-2 family proteins induces hepatocyte apoptosis manage preferences content mitochondrial implication cell growth article cite apoptosis evolution caspase activation https nicotera rights optional cookies article choices essential cookies cookies skip //doi

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         headline:Mitochondrial implication in apoptosis. Towards an endosymbiont hypothesis of apoptosis evolution
         description:Recent evidence indicates that a profound alteration in mitochondrial function constitutes an obligatory early event of the apoptotic process. The molecular mechanism accounting for this alteration is mitochondrial permeability transition (PT). PT is both sufficient and necessary for apoptosis to occur. Experiments performed in cell-free systems of apoptosis demonstrate that mitochondria undergoing PT release protease activators that can trigger nuclear manifestations of apoptotis. Bcl-2 and its homologs are endogenous regulators of PT. It appears that some types of necrosis, those inhibited by Bcl-2, involve PT. If PT is a rate-limiting event of both apoptosis and necrosis, then downstream events including caspase activation and the bioenergetic consequences of PT must determine the choice between both modes of cell death. PT without caspase activation would cause necrosis. These findings have important implications for the comprehension of the apoptotic process, for the dichotomy between apoptosis and necrosis, and for the phylogeny of programmed cell death. Apoptosis may have evolved together with the endosymbiotic incorporation of aerobic bacteria (the precursors of mitochondria) into ancestral unicellular eukaryotes.
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      headline:Mitochondrial implication in apoptosis. Towards an endosymbiont hypothesis of apoptosis evolution
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