The role of mitochondria in cell metabolism and survival is controlled by calcium signals that are commonly transmitted at the close associations between mitochondria and endoplasmic reticulum (ER). However, the physical linkage of the ER–mitochondria interface and its relevance for cell function remains elusive. We show by electron tomography that ER and mitochondria are adjoined by tethers that are ∼10 nm at the smooth ER and ∼25 nm at the rough ER. Limited proteolysis separates ER from mitochondria, whereas expression of a short “synthetic linker” (<5 nm) leads to tightening of the associations. Although normal connections are necessary and sufficient for proper propagation of ER-derived calcium signals to the mitochondria, tightened connections, synthetic or naturally observed under apoptosis-inducing conditions, make mitochondria prone to Ca2+ overloading and ensuing permeability transition. These results reveal an unexpected dependence of cell function and survival on the maintenance of proper spacing between the ER and mitochondria.
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25 September 2006
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September 18 2006
Structural and functional features and significance of the physical linkage between ER and mitochondria
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JCB65: Mitochondria
György Csordás,
György Csordás
1Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107
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Christian Renken,
Christian Renken
2Resource for Visualization of Biological Complexity, Wadsworth Center, Albany, NY 12201
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Péter Várnai,
Péter Várnai
3Endocrinology and Reproduction Research Branch, National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
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Ludivine Walter,
Ludivine Walter
1Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107
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David Weaver,
David Weaver
1Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107
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Karolyn F. Buttle,
Karolyn F. Buttle
2Resource for Visualization of Biological Complexity, Wadsworth Center, Albany, NY 12201
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Tamás Balla,
Tamás Balla
3Endocrinology and Reproduction Research Branch, National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
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Carmen A. Mannella,
Carmen A. Mannella
2Resource for Visualization of Biological Complexity, Wadsworth Center, Albany, NY 12201
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György Hajnóczky
György Hajnóczky
1Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107
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György Csordás
1Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107
Christian Renken
2Resource for Visualization of Biological Complexity, Wadsworth Center, Albany, NY 12201
Péter Várnai
3Endocrinology and Reproduction Research Branch, National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
Ludivine Walter
1Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107
David Weaver
1Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107
Karolyn F. Buttle
2Resource for Visualization of Biological Complexity, Wadsworth Center, Albany, NY 12201
Tamás Balla
3Endocrinology and Reproduction Research Branch, National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892
Carmen A. Mannella
2Resource for Visualization of Biological Complexity, Wadsworth Center, Albany, NY 12201
György Hajnóczky
1Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107
Correspondence to György Hajnóczky: [email protected]
Abbreviations used in this paper: [Ca2+]c, cytoplasmic [Ca2+]; [Ca2+]m, mitochondrial matrix [Ca2+]; ET, electron tomography; IP3R, IP3 receptor; mRFP, monomeric red fluorescent protein; OMM, outer mitochondrial membrane; SBI, soybean trypsin inhibitor; TEM, transmission EM; Tg, thapsigargin.
Received:
April 05 2006
Accepted:
August 15 2006
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2006
J Cell Biol (2006) 174 (7): 915–921.
Article history
Received:
April 05 2006
Accepted:
August 15 2006
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György Csordás, Christian Renken, Péter Várnai, Ludivine Walter, David Weaver, Karolyn F. Buttle, Tamás Balla, Carmen A. Mannella, György Hajnóczky; Structural and functional features and significance of the physical linkage between ER and mitochondria . J Cell Biol 25 September 2006; 174 (7): 915–921. doi: https://doi.org/10.1083/jcb.200604016
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