title: Structural and functional features and significance of the physical linkage between ER and mitochondria.
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 approximately 10 nm at the smooth ER and approximately 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.
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: György
authors.initials: G
authors.lastname: Csordás
authors.forename: Christian
authors.initials: C
authors.lastname: Renken
authors.forename: Péter
authors.initials: P
authors.lastname: Várnai
authors.forename: Ludivine
authors.initials: L
authors.lastname: Walter
authors.forename: David
authors.initials: D
authors.lastname: Weaver
authors.forename: Karolyn F
authors.initials: KF
authors.lastname: Buttle
authors.forename: Tamás
authors.initials: T
authors.lastname: Balla
authors.forename: Carmen A
authors.initials: CA
authors.lastname: Mannella
authors.forename: György
authors.initials: G
authors.lastname: Hajnóczky
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002458:Cell Fractionation; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure*; D008930:Mitochondria, Liver / Q000378:metabolism* / Q000648:ultrastructure*; D008954:Models, Biological; D008969:Molecular Sequence Data; D051381:Rats; D014057:Tomography, X-Ray Computed
chemical_list: D002118:Calcium