A brain-specific isoform of mitochondrial apoptosis-inducing factor: AIF2

E. Hangen, D. De Zio, M. Bordi, C. Zhu, P. Dessen, F. Caffin, S. Lachkar, J. L. Perfettini, V. Lazar, J. Benard, G. M. Fimia, M. Piacentini, F. Harper, G. Pierron, J. M. Vicencio, P. Bénit, A. De Andrade, G. Höglinger, C. Culmsee, P. RustinK. Blomgren, F. Cecconi, G. Kroemer, N. Modjtahedi

Research output: Contribution to journalArticle

Abstract

Apoptosis-inducing factor (AIF) has 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. In this study, 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 in which they anchor to the inner membrane facing the intermembrane space. However, the mitochondrial inner membrane sorting signal 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 on 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.

Original languageEnglish
Pages (from-to)1155-1166
Number of pages12
JournalCell Death and Differentiation
Volume17
Issue number7
DOIs
Publication statusPublished - Jul 2010

Keywords

  • Brain development
  • Neural differentiation
  • Neural progenitor
  • Neuroblastoma
  • Oxidative phosphorylation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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    Hangen, E., De Zio, D., Bordi, M., Zhu, C., Dessen, P., Caffin, F., Lachkar, S., Perfettini, J. L., Lazar, V., Benard, J., Fimia, G. M., Piacentini, M., Harper, F., Pierron, G., Vicencio, J. M., Bénit, P., De Andrade, A., Höglinger, G., Culmsee, C., ... Modjtahedi, N. (2010). A brain-specific isoform of mitochondrial apoptosis-inducing factor: AIF2. Cell Death and Differentiation, 17(7), 1155-1166. https://doi.org/10.1038/cdd.2009.211