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Article Dans Une Revue Cell Death and Differentiation Année : 2010

A brain-specific isoform of mitochondrial Apoptosis Inducing Factor: AIF2

Philippe Dessen
Jean-Luc Perfettini
Nazanine Modjtahedi

Résumé

Apoptosis-Inducing factor (AIF) plays important supportive as well as potentially lethal roles in neurons. Under normal physiological conditions, AIF is a vital redox-active mitochondrial enzyme, whereas in pathological situations, it translocates from mitochondria to the nuclei of injured neurons and mediates apoptotic chromatin condensation and cell death. Here, we reveal the existence of a brain-specific isoform of AIF, AIF2, whose expression increases as neuronal precursor cells differentiate. AIF2 arises from the utilization of the alternative exon 2b, yet uses the same remaining 15 exons as the ubiquitous AIF1 isoform. AIF1 and AIF2 are similarly imported to mitochondria where they anchor to the inner membrane facing the intermembrane space. However, the mitochondrial inner membrane sorting signal (IMSS) encoded in the exon 2b of AIF2 is more hydrophobic than that of AIF1, indicating a stronger membrane anchorage of AIF2 than AIF1. AIF2 is more difficult to be desorbed from mitochondria than AIF1 upon exposure to non-ionic detergents or basic pH. Furthermore, AIF2 dimerizes with AIF1, thereby preventing its release from mitochondria. Conversely, it is conceivable that a neuron-specific AIF isoform, AIF2, may have been "designed" to be retained in mitochondria and to minimize its potential neurotoxic activity.
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Dates et versions

hal-00506796 , version 1 (29-07-2010)

Identifiants

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Emilie Hangen, Daniela de Zio, Matteo Bordi, Changlian Zhu, Philippe Dessen, et al.. A brain-specific isoform of mitochondrial Apoptosis Inducing Factor: AIF2. Cell Death and Differentiation, 2010, 17, pp.1155-1166. ⟨10.1038/cdd.2009.211⟩. ⟨hal-00506796⟩
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