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Despite a tide of data suggesting that mitochondria are primary in triggering programmed cell death, a small minority of researchers argues that the primary apoptosis signals route directly to enzymes called caspases without first involving the mitochondria. The debate is hard to resolve because the events of apoptosis unfold too rapidly to determine their temporal sequence, and the use of techniques such as knocking out the genes for various components of the apoptosis pathways has provided fuel for both sides. The question is more than academic, as defects in apoptosis contribute to many major diseases; knowing exactly how to turn apoptosis on or off is therefore key to developing drugs to treat diseases in which it goes awry.
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