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Fis1 and Bap31 bridge the mitochondria–ER interface to establish a platform for apoptosis induction

Ryota Iwasawa, Anne‐Laure Mahul‐Mellier, Christoph Datler, Evangelos Pazarentzos, Stefan Grimm

Author Affiliations

  1. Ryota Iwasawa1,
  2. Anne‐Laure Mahul‐Mellier1,
  3. Christoph Datler1,
  4. Evangelos Pazarentzos1 and
  5. Stefan Grimm*,1
  1. 1 Division of Experimental Medicine, Centre for Pharmacology and Therapeutics, Imperial College London, London, UK
  1. *Corresponding author. Division of Experimental Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK. Tel.: +44 20 7594 6898; Fax: +44 20 7594 7393; E-mail: s.grimm{at}imperial.ac.uk
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Abstract

The mitochondria and the endoplasmic reticulum (ER) are two organelles that critically contribute to apoptosis induction. While it is established that they communicate, how cell death signals are transmitted from the mitochondria to the ER is unknown. Here, we show that the mitochondrial fission protein Fission 1 homologue (Fis1) conveys an apoptosis signal from the mitochondria to the ER by interacting with Bap31 at the ER and facilitating its cleavage into the pro‐apoptotic p20Bap31. Exogenous apoptosis inducers likewise use this signalling route and induce the procession of Bap31. Moreover, we show that the recruitment of procaspase‐8 to the Fis1–Bap31 platform is an early event during apoptosis induction. The association of procaspase‐8 with the Fis1–Bap31 complex is dependent on the variant of death effector domain (vDED) in Bap31 and is required for the activation of procaspase‐8. This signalling pathway establishes a feedback loop by releasing Ca2+ from the ER that activates the mitochondria for apoptosis. Hence, the Fis1–Bap31 complex (ARCosome) that spans the mitochondria–ER interface serves as a platform to activate the initiator procaspase‐8, and thereby bridges two critical organelles for apoptosis signalling.

There is a Have you seen? (February 2011) associated with this Article.

  • Received November 5, 2010.
  • Accepted December 8, 2010.
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