Alix is involved in caspase 9 activation during calcium-induced apoptosis

Flavie Strappazzon, Sakina Torch, Christine Chatellard-Causse, Anne Petiot, Chantal Thibert, Béatrice Blot, Jean Marc Verna, Rémy Sadoul

Research output: Contribution to journalArticle

Abstract

The cytoplasmic protein Alix/AIP1 (ALG-2 interacting protein X) is involved in cell death through mechanisms which remain unclear but require its binding partner ALG-2 (apoptosis-linked gene-2). The latter was defined as a regulator of calcium-induced apoptosis following endoplasmic reticulum (ER) stress. We show here that Alix is also a critical component of caspase 9 activation and apoptosis triggered by calcium. Indeed, expression of Alix dominant-negative mutants or downregulation of Alix afford significant protection against cytosolic calcium elevation following thapsigargin (Tg) treatment. The function of Alix in this paradigm requires its interaction with ALG-2. In addition, we demonstrate that caspase 9 activation is necessary for apoptosis induced by Tg and that this activation is impaired by knocking down Alix. Altogether, our findings identify, for the first time, Alix as a crucial mediator of Ca2+ induced caspase 9 activation.

Original languageEnglish
Pages (from-to)64-69
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume397
Issue number1
DOIs
Publication statusPublished - Jun 18 2010

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Keywords

  • ALG-2
  • Apoptosis
  • Cell death
  • Cerebellar granule neurons
  • Endoplasmic reticulum
  • Thapsigargin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Strappazzon, F., Torch, S., Chatellard-Causse, C., Petiot, A., Thibert, C., Blot, B., Verna, J. M., & Sadoul, R. (2010). Alix is involved in caspase 9 activation during calcium-induced apoptosis. Biochemical and Biophysical Research Communications, 397(1), 64-69. https://doi.org/10.1016/j.bbrc.2010.05.062