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Perspectives
AIF-Mediated Programmed Necrosis: A Highly Orchestrated Way to Die
Hanan Boujrad, Olena Gubkina, Nadine Robert, Slavica Krantic and Santos A. Susin
volume 6 | issue 21
1 November 2007Pages: 2612 - 2619
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Historically, two main forms of cell death have been distinguished: apoptosis and necrosis. Apoptosis was initially considered as the only physiological and programmed form of cell death. This type of death is recurrently associated with caspases, a family of cysteine proteases activated in apoptotic conditions. However, it is now widely recognized that programmed cell death (PCD) can also occur in the complete absence of caspase activation. The existence of non-caspase PCD pathways was corroborated by the discovery of caspase-independent executioners, such as the mitochondrial protein Apoptosis-Inducing Factor (AIF). Necrosis has often been viewed as an accidental and uncontrolled cell death process. Nevertheless, increasing evidence shows that, like apoptosis, necrosis could be a highly regulated type of PCD. Indeed, apoptosis and necrosis present more similarities than it has been originally thought. Here, we summarize the different classifications of PCD and the current knowledge of a necrotic PCD pathway mediated by AIF: alkylating DNA-damage mediated death. We also outline the molecular mechanisms controlling this form of PCD and discuss their potential relevance in physiological and pathological settings. These emerging data on the molecular mechanisms regulating programmed necrosis may certainly have potent therapeutic consequences in treating both apoptotic-resistant tumors and degenerating adult neurons.
Authors
Hanan Boujrad
Institut Pasteur; Paris, France
Olena Gubkina
Parc Scientifique de Luminy; Marseille, France
Nadine Robert
Institut Pasteur; Paris, France
Slavica Krantic
Parc Scientifique de Luminy; Marseille, France
Santos A. Susin
Institut Pasteur; Paris, France