Specific ablation of the apoptotic functions of cytochrome C reveals a differential requirement for cytochrome C and Apaf-1 in apoptosis - PubMed (original) (raw)

. 2005 May 20;121(4):579-591.

doi: 10.1016/j.cell.2005.03.016.

Gordon S Duncan 2, Chia-Che Chang 2, Andrew Elia 2, Min Fang 3, Andrew Wakeham 2, Hitoshi Okada 2, Thomas Calzascia 2, YingJu Jang 2, Annick You-Ten 2, Wen-Chen Yeh 2, Pamela Ohashi 2, Xiaodong Wang 3, Tak W Mak 4

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Specific ablation of the apoptotic functions of cytochrome C reveals a differential requirement for cytochrome C and Apaf-1 in apoptosis

Zhenyue Hao et al. Cell. 2005.

Free article

Abstract

As components of the apoptosome, a caspase-activating complex, cytochrome c (Cyt c) and Apaf-1 are thought to play critical roles during apoptosis. Due to the obligate function of Cyt c in electron transport, its requirement for apoptosis in animals has been difficult to establish. We generated "knockin" mice expressing a mutant Cyt c (KA allele), which retains normal electron transfer function but fails to activate Apaf-1. Most KA/KA mice displayed embryonic or perinatal lethality caused by defects in the central nervous system, and surviving mice exhibited impaired lymphocyte homeostasis. Although fibroblasts from the KA/KA mice were resistant to apoptosis, their thymocytes were markedly more sensitive to death stimuli than Apaf-1(-/-) thymocytes. Upon treatment with gamma irradiation, procaspases were efficiently activated in apoptotic KA/KA thymocytes, but Apaf-1 oligomerization was not observed. These studies indicate the existence of a Cyt c- and apoptosome-independent but Apaf-1-dependent mechanism(s) for caspase activation.

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