Bcl-2 decreases the free Ca2+ concentration within the endoplasmic reticulum
R Foyouzi-Youssefi1, S Arnaudeau, C Borner
1Departments of Geriatrics and Physiology and Division of Infectious Diseases, Geneva Medical School, 1211 Geneva 14, Switzerland. Reyhaneh.Foyouzi@hcuge.ch
Summary
The antiapoptotic protein Bcl-2 reduces endoplasmic reticulum (ER) calcium storage by increasing ER membrane permeability. This suggests Bcl-2 may function as an ion channel in the ER.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The antiapoptotic protein Bcl-2 is found in mitochondria and the endoplasmic reticulum (ER).
- The specific function of Bcl-2 within the ER remains largely unknown.
- Calcium (Ca2+) signaling is crucial for various cellular processes, with the ER serving as a major Ca2+ store.
Purpose of the Study:
- To investigate the impact of Bcl-2 expression on Ca2+ storage and release from the ER.
- To elucidate the mechanism by which Bcl-2 influences intracellular Ca2+ dynamics at the ER level.
Main Methods:
- Measuring Ca2+ release from intracellular stores under various depletion conditions.
- Utilizing ER-targeted Ca2+-sensitive fluorescent proteins (cameleon) to assess luminal ER Ca2+ concentrations ([Ca2+](ER)).
- Analyzing Ca2+ store depletion kinetics using the Ca2+-ATPase inhibitor thapsigargin.
Main Results:
- Bcl-2 expression consistently reduced Ca2+ release from intracellular stores.
- Bcl-2 decreased cellular Ca2+ store content independently of mitochondrial Ca2+ uptake.
- Direct measurements showed Bcl-2 lowers the free Ca2+ concentration within the ER lumen ([Ca2+](ER)).
- Bcl-2 was found to increase the permeability of the ER membrane to Ca2+.
Conclusions:
- Bcl-2 reduces luminal ER Ca2+ concentration by increasing ER membrane permeability.
- The observed increase in ER Ca2+ permeability suggests a potential ion channel function for Bcl-2 at the ER membrane.
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