期刊
JOURNAL OF BIOENERGETICS AND BIOMEMBRANES
卷 46, 期 1, 页码 1-15出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10863-013-9527-7
关键词
Calcium signaling; Apoptosis; Bcl-2; Mitochondria-associated ER membrane (MAM); Bioenergetics; ER; Mitochondria; Inositol 1,4,5-trisphosphate receptor (IP3R)
资金
- Intramural Research Program of the National Institute on Drug Abuse
- National Institutes of Health
- Department of Health and Human Services
Bcl-2 family proteins, known for their apoptosis functioning at the mitochondria, have been shown to localize to other cellular compartments to mediate calcium (Ca2+) signals. Since the proper supply of Ca2+ in cells serves as an important mechanism for cellular survival and bioenergetics, we propose an integrating role for Bcl-2 family proteins in modulating Ca2+ signaling. The endoplasmic reticulum (ER) is the main Ca2+ storage for the cell and Bcl-2 family proteins competitively regulate its Ca2+ concentration. Bcl-2 family proteins also regulate the flux of Ca2+ from the ER by physically interacting with inositol 1,4,5-trisphosphate receptors (IP(3)Rs) to mediate their opening. Type 1 IP(3)Rs reside at the bulk ER to coordinate cytosolic Ca2+ signals, while type 3 IP(3)Rs reside at mitochondria-associated ER membrane (MAM) to facilitate mitochondrial Ca2+ uptake. In healthy cells, mitochondrial Ca2+ drives pyruvate into the citric acid (TCA) cycle to facilitate ATP production, while a continuous accumulation of Ca2+ can trigger the release of cytochrome c, thus initiating apoptosis. Since multiple organelles and Bcl-2 family proteins are involved in Ca2+ signaling, we aim to clarify the role that Bcl-2 family proteins play in facilitating Ca2+ signaling and how mitochondrial Ca2+ is relevant in both bioenergetics and apoptosis. We also explore how these insights could be useful in controlling bioenergetics in apoptosis-resistant cell lines.
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