Bcl-2-Protein Family as Modulators of IP3 Receptors and Other Organellar Ca2+ Channels

The pro- and antiapoptotic proteins belonging to the B-cell lymphoma-2 (Bcl-2) family exert a critical control over cell-death processes by enabling or counteracting mitochondrial outer membrane permeabilization. Beyond this mitochondrial function, several Bcl-2 family members have emerged as critic...

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Bibliographic Details
Published in:Cold Spring Harbor perspectives in biology 2020-04, Vol.12 (4)
Main Authors: Ivanova, Hristina, Vervliet, Tim, Monaco, Giovanni, Terry, Lara E, Rosa, Nicolas, Baker, Mariah R, Parys, Jan B, Serysheva, Irina I, Yule, David I, Bultynck, Geert
Format: Article
Language:English
Subjects:
Amino acid sequence
Anion channels
Apoptosis
Bcl-2 protein
Calcium (intracellular)
Calcium (mitochondrial)
Calcium (reticular)
Calcium channels
Calcium homeostasis
Calcium ions
Calcium release channels
Calcium signalling
Calcium transport
Cell death
Endoplasmic reticulum
Homeostasis
Inositol 1,4,5-trisphosphate receptors
Intracellular
Ion channels
Lymphocytes B
Lymphoma
Membranes
Mitochondria
Modulators
Molecular structure
PERSPECTIVES
Proteins
Receptors
Ryanodine receptors
Transportation systems
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Summary:The pro- and antiapoptotic proteins belonging to the B-cell lymphoma-2 (Bcl-2) family exert a critical control over cell-death processes by enabling or counteracting mitochondrial outer membrane permeabilization. Beyond this mitochondrial function, several Bcl-2 family members have emerged as critical modulators of intracellular Ca2+ homeostasis and dynamics, showing proapoptotic and antiapoptotic functions. Bcl-2 family proteins specifically target several intracellular Ca2+-transport systems, including organellar Ca2+ channels: inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs), Ca2+-release channels mediating Ca2+ flux from the endoplasmic reticulum, as well as voltage-dependent anion channels (VDACs), which mediate Ca2+ flux across the mitochondrial outer membrane into the mitochondria. Although the formation of protein complexes between Bcl-2 proteins and these channels has been extensively studied, a major advance during recent years has been elucidating the complex interaction of Bcl-2 proteins with IP3Rs. Distinct interaction sites for different Bcl-2 family members were identified in the primary structure of IP3Rs. The unique molecular profiles of these Bcl-2 proteins may account for their distinct functional outcomes when bound to IP3Rs. Furthermore, Bcl-2 inhibitors used in cancer therapy may affect IP3R function as part of their proapoptotic effect and/or as an adverse effect in healthy cells.
ISSN:1943-0264
DOI:10.1101/cshperspect.a035089