Structural and functional features and significance of the physical linkage between ER and mitochondria

By G. Csordás, C. Renken, P. Várnai, L. Walter, David B. Weaver, K. Buttle, T. Balla, C. Mannella, G. Hajnóczky. Journal of Cell Biology, 2006

1,347 citations recorded by the source corpus.

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.

Subfields: Clinical Biochemistry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ef2671306c543ab1ca50f325870bceb7bf927f8c

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Clinical Biochemistry

J. Vance

In Molecular Biology

Citations in the corpus

MAM (2009, background): “The association is, however, sensitive to Ca2+ [11,13].”
Mitochondria-lysosome contacts regulate mitochondrial fission via Rab7 GTP hydrolysis (2018, neutral): “1a–c, yellow arrows) with an average distance between membranes of 9.57 ± 0.76 nm consistent with other contact sites 21,22 , and contact length of 198.33 ± 16.73 nm (n = 55 contacts from 20 cells) (Fig.”
Imaging interorganelle contacts and local calcium dynamics at the ER-mitochondrial interface (2010, positive): “At the end of the recording, rhod2 was calibrated using sequential addition of CaCl2 (1 mM) and EGTA/ Tris (10 mM, pH 8.7), and [Ca2+]c was calculated in nM using a KD value of 1 mM as described earlier (Csordás and Hajnóczky, 2003; Csordás et al., 2006).”
Phospholipid Synthesis and Transport in Mammalian Cells (2015, background): “High-resolution electron microscopy showed that the distance between the ER and mitochondrial outer membranes at these contact sites in mammalian cells is 10–30 nm (76,77), a separation that could accommodate an inter-organelle protein bridge.”
Lipids of mitochondria. (2013, background): “Association and tethering between the two organelles is important for cell function and survival [275].”
Essential regulation of cell bioenergetics by constitutive InsP3 receptor Ca2+ transfer to mitochondria. (2010, positive): “Nevertheless, InsP3-linked agonists that generate sub-mM global [Ca2+]i elevations trigger large increases in mitochondrial matrix [Ca2+] (Spat et al., 2008) because of close appositions between mitochondria and ER supported by physical linkages (Csordas et al., 2006; Rizzuto et al., 1998).”