Modulation of Ca2+ Signaling by Anti-apoptotic B-Cell Lymphoma 2 Proteins at the Endoplasmic Reticulum–Mitochondrial Interface
Mitochondria are important regulators of cell death and cell survival. Mitochondrial Ca2+ levels are critically involved in both of these processes. On the one hand, excessive mitochondrial Ca2+ leads to Ca2+-induced mitochondrial outer membrane permeabilization and thus apoptosis. On the other hand...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fonc.2017.00075/full |
| _version_ | 1819136629977120768 |
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| author | Tim Vervliet Eva Clerix Bruno Seitaj Hristina Ivanova Giovanni Monaco Geert Bultynck |
| author_facet | Tim Vervliet Eva Clerix Bruno Seitaj Hristina Ivanova Giovanni Monaco Geert Bultynck |
| author_sort | Tim Vervliet |
| collection | DOAJ |
| description | Mitochondria are important regulators of cell death and cell survival. Mitochondrial Ca2+ levels are critically involved in both of these processes. On the one hand, excessive mitochondrial Ca2+ leads to Ca2+-induced mitochondrial outer membrane permeabilization and thus apoptosis. On the other hand, mitochondria need Ca2+ in order to efficiently fuel the tricarboxylic acid cycle and maintain adequate mitochondrial bioenergetics. For obtaining this Ca2+, the mitochondria are largely dependent on close contact sites with the endoplasmic reticulum (ER), the so-called mitochondria-associated ER membranes. There, the inositol 1,4,5-trisphosphate receptors are responsible for the Ca2+ release from the ER. It comes as no surprise that this Ca2+ release from the ER and the subsequent Ca2+ uptake at the mitochondria are finely regulated. Cancer cells often modulate ER-Ca2+ transfer to the mitochondria in order to promote cell survival and to inhibit cell death. Important regulators of these Ca2+ signals and the onset of cancer are the B-cell lymphoma 2 (Bcl-2) family of proteins. An increasing number of reports highlight the ability of these Bcl-2-protein family members to finely regulate Ca2+ transfer from ER to mitochondria both in healthy cells and in cancer. In this review, we focus on recent insights into the dynamic regulation of ER–mitochondrial Ca2+ fluxes by Bcl-2-family members and how this impacts cell survival, cell death and mitochondrial energy production. |
| first_indexed | 2024-12-22T10:38:02Z |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-22T10:38:02Z |
| publishDate | 2017-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-56dcfda9315e4bab8b1c1bc34f4beff42022-12-21T18:29:06ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2017-05-01710.3389/fonc.2017.00075255511Modulation of Ca2+ Signaling by Anti-apoptotic B-Cell Lymphoma 2 Proteins at the Endoplasmic Reticulum–Mitochondrial InterfaceTim Vervliet0Eva Clerix1Bruno Seitaj2Hristina Ivanova3Giovanni Monaco4Geert Bultynck5Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, BelgiumLaboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, BelgiumLaboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, BelgiumLaboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, BelgiumLaboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, BelgiumLaboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, BelgiumMitochondria are important regulators of cell death and cell survival. Mitochondrial Ca2+ levels are critically involved in both of these processes. On the one hand, excessive mitochondrial Ca2+ leads to Ca2+-induced mitochondrial outer membrane permeabilization and thus apoptosis. On the other hand, mitochondria need Ca2+ in order to efficiently fuel the tricarboxylic acid cycle and maintain adequate mitochondrial bioenergetics. For obtaining this Ca2+, the mitochondria are largely dependent on close contact sites with the endoplasmic reticulum (ER), the so-called mitochondria-associated ER membranes. There, the inositol 1,4,5-trisphosphate receptors are responsible for the Ca2+ release from the ER. It comes as no surprise that this Ca2+ release from the ER and the subsequent Ca2+ uptake at the mitochondria are finely regulated. Cancer cells often modulate ER-Ca2+ transfer to the mitochondria in order to promote cell survival and to inhibit cell death. Important regulators of these Ca2+ signals and the onset of cancer are the B-cell lymphoma 2 (Bcl-2) family of proteins. An increasing number of reports highlight the ability of these Bcl-2-protein family members to finely regulate Ca2+ transfer from ER to mitochondria both in healthy cells and in cancer. In this review, we focus on recent insights into the dynamic regulation of ER–mitochondrial Ca2+ fluxes by Bcl-2-family members and how this impacts cell survival, cell death and mitochondrial energy production.http://journal.frontiersin.org/article/10.3389/fonc.2017.00075/fullendoplasmic reticulum–mitochondria contact sitesCa2+-transport systemsapoptosisautophagymitochondrial bio energeticsIP3 receptors |
| spellingShingle | Tim Vervliet Eva Clerix Bruno Seitaj Hristina Ivanova Giovanni Monaco Geert Bultynck Modulation of Ca2+ Signaling by Anti-apoptotic B-Cell Lymphoma 2 Proteins at the Endoplasmic Reticulum–Mitochondrial Interface Frontiers in Oncology endoplasmic reticulum–mitochondria contact sites Ca2+-transport systems apoptosis autophagy mitochondrial bio energetics IP3 receptors |
| title | Modulation of Ca2+ Signaling by Anti-apoptotic B-Cell Lymphoma 2 Proteins at the Endoplasmic Reticulum–Mitochondrial Interface |
| title_full | Modulation of Ca2+ Signaling by Anti-apoptotic B-Cell Lymphoma 2 Proteins at the Endoplasmic Reticulum–Mitochondrial Interface |
| title_fullStr | Modulation of Ca2+ Signaling by Anti-apoptotic B-Cell Lymphoma 2 Proteins at the Endoplasmic Reticulum–Mitochondrial Interface |
| title_full_unstemmed | Modulation of Ca2+ Signaling by Anti-apoptotic B-Cell Lymphoma 2 Proteins at the Endoplasmic Reticulum–Mitochondrial Interface |
| title_short | Modulation of Ca2+ Signaling by Anti-apoptotic B-Cell Lymphoma 2 Proteins at the Endoplasmic Reticulum–Mitochondrial Interface |
| title_sort | modulation of ca2 signaling by anti apoptotic b cell lymphoma 2 proteins at the endoplasmic reticulum mitochondrial interface |
| topic | endoplasmic reticulum–mitochondria contact sites Ca2+-transport systems apoptosis autophagy mitochondrial bio energetics IP3 receptors |
| url | http://journal.frontiersin.org/article/10.3389/fonc.2017.00075/full |
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