Fis1 and Bap31 bridge the mitochondria–ER interface to establish a platform for apoptosis induction
Open accessAbstract
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 Ca(2+) 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.
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Other important MAM tethering proteins are B-cell receptor-associated protein 31, mitochondrial fission 1 protein, and mitofusin.
“Other important MAM tethering proteins are B-cell receptor–associated protein 31, mitochondrial fission 1 protein [96], and mitofusin [97].”
From Neuronal Apolipoprotein E4 Expression Results in Proteome-Wide Alterations and Compromises Bioenergetic Capacity by Disrupting Mitochondrial Function (2019) · cites this paper as [96]
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- Authors
- Iwasawa, R., Mahul‐Mellier, A., Datler, C., Pazarentzos, E., & Grimm, S.
- Affiliations
- Imperial College London (GB)
- Corresponding author
- Grimm, Stefan
- Venue
- The EMBO Journal
- Published
- 2010-12-24
- Volume
- 30
- Issue
- 3
- Pages
- 556-568
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC3034017
- OpenAlex
- W2146403365
- Cited by
- 520
- References
- 4
- Citations by year
- 2026: 24 · 2025: 37 · 2024: 46 · 2023: 46 · 2022: 47 · 2021: 48 · 2020: 42 · 2019: 29 · 2018: 29 · 2017: 33 · 2016: 24 · 2015: 28 · 2014: 28 · 2013: 21 · 2012: 21
- FWCI
- 7.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Imperial College Research Computing Service Data Repository
- Funders
- Cancer Research UK
- Breast Cancer Campaign
- Imperial College London
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Keywords
- Fis1, BAP31, apoptosis signaling, mitochondrial fission, initiator caspases
- MeSH terms
- Calcium, Endoplasmic Reticulum, Genetic Vectors, Humans, Membrane Proteins, Microscopy, Fluorescence, Mitochondria, Models, Biological, Permeability, Transfection, Immunoblotting, Signal Transduction, Apoptosis, DNA Primers, Mitochondrial Proteins, Multiprotein Complexes, Immunoprecipitation, Mitochondrial Membranes, Caspase 8
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