Crossref journal-article
Rockefeller University Press
The Journal of Cell Biology (291)
Abstract

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.

Bibliography

Csordás, G., Renken, C., Várnai, P., Walter, L., Weaver, D., Buttle, K. F., Balla, T., Mannella, C. A., & Hajnóczky, G. (2006). Structural and functional features and significance of the physical linkage between ER and mitochondria. The Journal of Cell Biology, 174(7), 915–921.

Authors 9
  1. György Csordás (first)
  2. Christian Renken (additional)
  3. Péter Várnai (additional)
  4. Ludivine Walter (additional)
  5. David Weaver (additional)
  6. Karolyn F. Buttle (additional)
  7. Tamás Balla (additional)
  8. Carmen A. Mannella (additional)
  9. György Hajnóczky (additional)
References 36 Referenced 1,148
  1. 10.1152/physrev.1999.79.4.1127 / Physiol. Rev. (1999)
  2. 10.1074/jbc.274.29.20643 / J. Biol. Chem. (1999)
  3. 10.1042/BJ20050738 / Biochem. J. (2005)
  4. 10.1093/emboj/21.7.1616 / EMBO J. (2002)
  5. 10.1054/ceca.2000.0191 / Cell Calcium. (2001)
  6. 10.1093/emboj/18.1.96 / EMBO J. (1999)
  7. 10.1126/science.1083628 / Science. (2003)
  8. 10.1074/jbc.M412694200 / J. Biol. Chem. (2005)
  9. 10.1038/ncb1101-e255 / Nat. Cell Biol. (2001)
  10. 10.1074/jbc.M302301200 / J. Biol. Chem. (2003)
  11. 10.1006/jsbi.1996.0030 / J. Struct. Biol. (1996)
  12. 10.1126/science.1099320 / Science. (2004)
  13. 10.1016/0092-8674(95)90430-1 / Cell. (1995)
  14. 10.1073/pnas.180143997 / Proc. Natl. Acad. Sci. USA. (2000)
  15. 10.1073/pnas.96.24.13807 / Proc. Natl. Acad. Sci. USA. (1999)
  16. 10.1038/nature02246 / Nature. (2004)
  17. 10.1002/jemt.1070270403 / Microsc. Res. Tech. (1994)
  18. 10.1002/biof.5520080309 / Biofactors. (1998)
  19. 10.1006/jsbi.1996.0016 / J. Struct. Biol. (1996)
  20. 10.1016/0005-2736(81)90335-7 / Biochim. Biophys. Acta. (1981)
  21. 10.1016/j.ceca.2005.06.011 / Cell Calcium. (2005)
  22. 10.1111/j.1469-7793.2000.00553.x / J. Physiol. (2000)
  23. 10.1042/bj2080505 / Biochem. J. (1982)
  24. 10.1016/0304-3991(95)00078-X / Ultramicroscopy. (1995)
  25. 10.1091/mbc.10.12.4403 / Mol. Biol. Cell. (1999)
  26. 10.1083/jcb.200205091 / J. Cell Biol. (2002)
  27. 10.1126/science.280.5370.1763 / Science. (1998)
  28. 10.1093/emboj/17.17.4987 / EMBO J. (1998)
  29. 10.1083/jcb.72.3.714 / J. Cell Biol. (1977)
  30. 10.1038/sj.emboj.7600559 / EMBO J. (2005)
  31. 10.1242/jcs.01299 / J. Cell Sci. (2004)
  32. 10.1073/pnas.0407535102 / Proc. Natl. Acad. Sci. USA. (2005)
  33. 10.1016/j.tibs.2005.05.008 / Trends Biochem. Sci. (2005)
  34. 10.1083/jcb.150.6.1489 / J. Cell Biol. (2000)
  35. 10.1083/jcb.200406038 / J. Cell Biol. (2004)
  36. 10.1074/jbc.274.1.316 / J. Biol. Chem. (1999)
Dates
Type When
Created 18 years, 11 months ago (Sept. 18, 2006, 8:43 p.m.)
Deposited 2 years ago (July 29, 2023, 3:50 a.m.)
Indexed 9 hours, 28 minutes ago (Aug. 23, 2025, 9:38 p.m.)
Issued 18 years, 11 months ago (Sept. 18, 2006)
Published 18 years, 11 months ago (Sept. 18, 2006)
Published Online 18 years, 11 months ago (Sept. 18, 2006)
Published Print 18 years, 10 months ago (Sept. 25, 2006)
Funders 0

None

@article{Csorda_s_2006, title={Structural and functional features and significance of the physical linkage between ER and mitochondria}, volume={174}, ISSN={0021-9525}, url={http://dx.doi.org/10.1083/jcb.200604016}, DOI={10.1083/jcb.200604016}, number={7}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Csordás, György and Renken, Christian and Várnai, Péter and Walter, Ludivine and Weaver, David and Buttle, Karolyn F. and Balla, Tamás and Mannella, Carmen A. and Hajnóczky, György}, year={2006}, month=sep, pages={915–921} }