IRBIT controls apoptosis by interacting with the Bcl-2 homolog, Bcl2l10, and by promoting ER-mitochondria contact

Benjamin Bonneau, Hideaki Ando, Katsuhiro Kawaai, Matsumi Hirose, Hiromi Takahashi-Iwanaga, Katsuhiko Mikoshiba

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

IRBIT is a molecule that interacts with the inositol 1,4,5-trisphosphate (IP3)-binding pocket of the IP3 receptor (IP3R), whereas the antiapoptotic protein, Bcl2l10, binds to another part of the IP3-binding domain. Here we show that Bcl2l10 and IRBIT interact and exert an additive inhibition of IP3R in the physiological state. Moreover, we found that these proteins associate in a complex in mitochondria-associated membranes (MAMs) and that their interplay is involved in apoptosis regulation. MAMs are a hotspot for Ca2+ transfer between endoplasmic reticulum (ER) and mitochondria, and massive Ca2+ release through IP3R in mitochondria induces cell death. We found that upon apoptotic stress, IRBIT is dephosphorylated, becoming an inhibitor of Bcl2l10. Moreover, IRBIT promotes ER mitochondria contact. Our results suggest that by inhibiting Bcl2l10 activity and promoting contact between ER and mitochondria, IRBIT facilitates massive Ca2+ transfer to mitochondria and promotes apoptosis. This work then describes IRBIT as a new regulator of cell death.

Original languageEnglish
Article numbere19896
JournaleLife
Volume5
Issue numberDECEMBER2016
DOIs
Publication statusPublished - 2016 Dec 20
Externally publishedYes

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Mitochondria
Endoplasmic Reticulum
Apoptosis
Inositol 1,4,5-Trisphosphate Receptors
Cell death
Cell Death
Membranes
Inositol 1,4,5-Trisphosphate
Proteins
Molecules

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Bonneau, B., Ando, H., Kawaai, K., Hirose, M., Takahashi-Iwanaga, H., & Mikoshiba, K. (2016). IRBIT controls apoptosis by interacting with the Bcl-2 homolog, Bcl2l10, and by promoting ER-mitochondria contact. eLife, 5(DECEMBER2016), [e19896]. https://doi.org/10.7554/eLife.19896

IRBIT controls apoptosis by interacting with the Bcl-2 homolog, Bcl2l10, and by promoting ER-mitochondria contact. / Bonneau, Benjamin; Ando, Hideaki; Kawaai, Katsuhiro; Hirose, Matsumi; Takahashi-Iwanaga, Hiromi; Mikoshiba, Katsuhiko.

In: eLife, Vol. 5, No. DECEMBER2016, e19896, 20.12.2016.

Research output: Contribution to journalArticle

Bonneau, B, Ando, H, Kawaai, K, Hirose, M, Takahashi-Iwanaga, H & Mikoshiba, K 2016, 'IRBIT controls apoptosis by interacting with the Bcl-2 homolog, Bcl2l10, and by promoting ER-mitochondria contact', eLife, vol. 5, no. DECEMBER2016, e19896. https://doi.org/10.7554/eLife.19896
Bonneau, Benjamin ; Ando, Hideaki ; Kawaai, Katsuhiro ; Hirose, Matsumi ; Takahashi-Iwanaga, Hiromi ; Mikoshiba, Katsuhiko. / IRBIT controls apoptosis by interacting with the Bcl-2 homolog, Bcl2l10, and by promoting ER-mitochondria contact. In: eLife. 2016 ; Vol. 5, No. DECEMBER2016.
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