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

Cell Death and Differentiation
Emilie HangenNazanine Modjtahedi

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 'd...Continue Reading

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Citations

Sep 14, 2010·Cell Death and Differentiation·N ModjtahediG Kroemer
Sep 28, 2010·Antioxidants & Redox Signaling·Irina F Sevrioukova
Jan 20, 2016·Trends in Biochemical Sciences·Nazanine ModjtahediGuido Kroemer
Mar 31, 2011·Neurochemistry International·Sugela Blancas, Julio Moran
May 26, 2015·Molecular Cell·Emilie HangenNazanine Modjtahedi
Apr 4, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jeejabai RadhakrishnanRaúl J Gazmuri
Aug 30, 2020·Neural Regeneration Research·Juan RodriguezChanglian Zhu
Feb 28, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Camille ReinhardtNazanine Modjtahedi
Apr 16, 2021·Molecular Neurodegeneration·Shuiqiao LiuYingfei Wang

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