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Under the synergistic stress of ROS accumulation and Ca 2+ overload, this condition eventually induces sustained opening of the mitochondrial permeability transition pore (mPTP) ( Pathological opening of the mitochondrial permeability transition pore (mPTP) promotes the release of pro-apoptotic molecules such as cytochrome c (Cyt C) and Smac/DIABLO into the cytosol, thereby initiating the caspase-9mediated intrinsic apoptotic cascade and triggering cardiomyocyte death (Zorov et al., 2014)

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21 identified AIF as a mitochondrial flavoprotein and a mitochondrial effector of apoptotic cell death while looking for molecules that induce noncaspase-dependent apoptosis