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1: Cell Death Differ. 2006 Dec;13(12):2062-7. Epub 2006 May 26.
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Requirement of cytochrome c for apoptosis in human cells.

Matapurkar A, Lazebnik Y.

Cold Spring Harbor Laboratory, One Bungtown Rd, Cold Spring Harbor, NY 11724, USA.

During apoptosis, cytochrome c released from mitochondria activates Apaf-1, a cofactor of caspase-9. The evidence that cytochrome c can activate Apaf-1 is abundant, but the proof that cytochrome c is required for apoptosis is limited to two studies that used genetically modified mice. One of these studies concluded that in some tissues apoptosis may require Apaf-1 but not cytochrome c, which indicated the need to analyze the requirement of cytochrome c beyond the mouse models, and in human tumor cells in particular. In this study, we designed tools to silence cytochrome c expression in human cells and tested these tools in an experimental system of oncogenic transformation. We found that cytochrome c was required for apoptosis induced by both DNA damage and, unexpectedly, TNFalpha. Overall, this study established that cytochrome c is required for apoptosis in human cells and provided tools to dissect mechanisms of apoptosis in various experimental models.

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PMID: 16729029 [PubMed - indexed for MEDLINE]