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AMP kinase-mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis.

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posted on 04.04.2022, 14:48 by Caoimhín G. Concannon, Liam P. Tuffy, Petronela Weisová, Helena Bonner - GrehanHelena Bonner - Grehan, David Davila, Caroline Bonner, Marc DevocelleMarc Devocelle, Andreas Strasser, Manus W. Ward, Jochen PrehnJochen Prehn

Excitotoxicity after glutamate receptor overactivation induces disturbances in cellular ion gradients, resulting in necrosis or apoptosis. Excitotoxic necrosis is triggered by rapid, irreversible ATP depletion, whereas the ability to recover cellular bioenergetics is suggested to be necessary for the activation of excitotoxic apoptosis. In this study, we demonstrate that even a transient decrease in cellular bioenergetics and an associated activation of adenosine monophosphate-activated protein kinase (AMPK) is necessary for the activation of excitotoxic apoptosis. We show that the Bcl-2 homology domain 3 (BH3)-only protein Bim, a proapoptotic Bcl-2 family member, is activated in multiple excitotoxicity paradigms, mediates excitotoxic apoptosis, and inhibits delayed Ca(2+) deregulation, mitochondrial depolarization, and apoptosis-inducing factor translocation. We demonstrate that bim activation required the activation of AMPK and that prolonged AMPK activation is sufficient to induce bim gene expression and to trigger a bim-dependent cell death. Collectively, our data demonstrate that AMPK activation and the BH3-only protein Bim couple transient energy depletion to stress-induced neuronal apoptosis.

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The original article is available at http://jcb.rupress.org/content/189/1/83.full

Published Citation

Concannon CG, Tuffy LP, Weisová P, Bonner HP, Dávila D, Bonner C, Devocelle MC, Strasser A, Ward MW, Prehn JH. AMP kinase-mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis. J Cell Biol. 2010 Apr 5;189(1):83-94.

Publication Date

2010-04-05

PubMed ID

20351066

Department/Unit

  • Chemistry
  • Physiology and Medical Physics