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Mitochondria-associated ER Membranes (MAMs) and Glycosphingolipid Enriched Microdomains (GEMs): Isolation from Mouse Brain
Published on: March 4, 2013
Mitochondria and endoplasmic reticulum: the lethal interorganelle cross-talk
Ludivine Walter1, György Hajnóczky
1Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Abstract:
The fundamental contribution of the mitochondria and ER to the decision made on the cell's fate has been increasingly recognized. This progress has illuminated the need for the mechanisms these organelles use to initiate and to propagate apoptotic signals. The toolbox of the mitochondria and ER is evolutionary conserved, overlapping and complementary. Furthermore, mitochondria are often closely associated with the ER providing the conditions for a local and privileged communication between the two organelles. The present review is concerned with the spatially and temporally coordinated utilization of Bcl-2 family proteins and Ca(2+) by the mitochondria and ER to control the membrane permeabilization in the mitochondria and to regulate Ca(2+) distribution and the activity of apoptotic proteins in the ER. The apoptotic means of the mitochondria and ER will eventually come together to control the dismantling of the cell by the caspases and other enzymes.
Insights
Mitochondria and ER coordinate apoptotic signals using conserved mechanisms. Their interplay controls cell death pathways through Bcl-2 family proteins and calcium signaling, ultimately dismantling the cell.
Area of Science:
- Cell Biology
- Apoptosis Research
- Organelle Communication
Background:
- Mitochondria and endoplasmic reticulum (ER) roles in cell fate decisions are increasingly recognized.
- Understanding how these organelles initiate and propagate apoptotic signals is crucial.
- Mitochondria and ER possess overlapping, complementary, and evolutionarily conserved apoptotic mechanisms.
Purpose of the Study:
- To review the coordinated mechanisms of mitochondria and ER in apoptosis.
- To elucidate the roles of Bcl-2 family proteins and Ca(2+) in organelle-mediated cell death.
- To explain how these organelles control mitochondrial membrane permeabilization and ER-based apoptotic activity.
Main Methods:
- Review of existing literature on mitochondria-ER interactions in apoptosis.
- Analysis of the roles of Bcl-2 family proteins in regulating mitochondrial outer membrane permeabilization.
- Examination of calcium (Ca(2+)) signaling dynamics at the mitochondria-ER interface.
Main Results:
- Mitochondria and ER communicate closely, facilitating localized apoptotic signal propagation.
- Bcl-2 family proteins and Ca(2+) are key effectors utilized by both organelles.
- Coordinated action controls mitochondrial permeabilization and ER calcium homeostasis, impacting apoptosis.
Conclusions:
- The integrated apoptotic machinery of mitochondria and ER dictates cell fate decisions.
- Spatial and temporal coordination of Bcl-2 proteins and Ca(2+) is essential for effective apoptosis.
- These organelles converge to orchestrate cellular dismantling via caspases and other enzymes.
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