RRC ID 47693
著者 Bonneau B, Ando H, Kawaai K, Hirose M, Takahashi-Iwanaga H, Mikoshiba K.
タイトル IRBIT controls apoptosis by interacting with the Bcl-2 homolog, Bcl2l10, and by promoting ER-mitochondria contact.
ジャーナル Elife
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.
巻・号 5
公開日 2016-12-20
DOI 10.7554/eLife.19896
PII e19896
PMID 27995898
PMC PMC5173324
MeSH Animals Apoptosis* Cell Line Endoplasmic Reticulum / metabolism* Humans Inositol 1,4,5-Trisphosphate Receptors / antagonists & inhibitors Lectins, C-Type / metabolism* Membrane Proteins / metabolism* Mice Mitochondria / metabolism* Protein Binding Protein Interaction Mapping Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
IF 7.08
引用数 24
リソース情報
ヒト・動物細胞 HeLa(RCB0007)