Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death

Nicholas Joza, Santos A. Susin, Eric Daugas, William L. Stanford, Sarah K. Cho, Carol Y.J. Li, Takehiko Sasaki, Andrew J. Elia, H. Y.Mary Cheng, Luigi Ravagnan, Karine F. Ferri, Naoufal Zamzami, Andrew Wakeham, Razqallah Hakem, Hiroki Yoshida, Young Yun Kong, Tak W. Mak, Juan Carlos Zúñiga-Pflücker, Guido Kroemer, Josef M. Penninger

Résultats de recherche: Contribution à un journalArticleRevue par des pairs

1193 Citations (Scopus)

Résumé

Programmed cell death is a fundamental requirement for embryogenesis, organ metamorphosis and tissue homeostasis. In mammals, release of mitochondrial cytochrome c leads to the cytosolic assembly of the apoptosome - a caspase activation complex involving Apaf1 and caspase-9 that induces hallmarks of apoptosis. There are, however, mitochondrially regulated cell death pathways that are independent of Apaf1/caspase-9. We have previously cloned a molecule associated with programmed cell death called apoptosis-inducing factor (AIF). Like cytochrome c, AIF is localized to mitochondria and released in response to death stimuli. Here we show that genetic inactivation of AIF renders embryonic stem cells resistant to cell death after serum deprivation. Moreover, AIF is essential for programmed cell death during cavitation of embryoid bodies - the very first wave of cell death indispensable for mouse morphogenesis. AIF-dependent cell death displays structural features of apoptosis, and can be genetically uncoupled from Apaf1 and caspase-9 expression. Our data provide genetic evidence for a caspase-independent pathway of programmed cell death that controls early morphogenesis.

langue originaleAnglais
Pages (de - à)549-554
Nombre de pages6
journalNature
Volume410
Numéro de publication6828
Les DOIs
étatPublié - 29 mars 2001
Modification externeOui

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