Endoplasmic Reticulum-Mitochondrial Contactology: Structure and Signaling Functions

Trends Cell Biol. 2018 Jul;28(7):523-540. doi: 10.1016/j.tcb.2018.02.009. Epub 2018 Mar 24.


Interorganellar contacts are increasingly recognized as central to the control of cellular behavior. These contacts, which typically involve a small fraction of the endomembrane surface, are local communication hubs that resemble synapses. We propose the term contactology to denote the analysis of interorganellar contacts. Endoplasmic reticulum (ER) contacts with mitochondria were recognized several decades ago; major roles in ion and lipid transfer, signaling, and membrane dynamics have been established, while others continue to emerge. The functional diversity of ER-mitochondrial (ER-mito) contacts is mirrored in their structural heterogeneity, with subspecialization likely supported by multiple, different linker-forming protein structures. The nanoscale size of the contacts has made studying their structure, function, and dynamics difficult. This review focuses on the structure of the ER-mito contacts, methods for studying them, and the roles of contacts in Ca2+ and reactive oxygen species (ROS) signaling.

Keywords: IP3 receptor; calcium ion; linkers; mitochondrion-associated membrane; ryanodine receptor; sarcoplasmic reticulum.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium / chemistry
  • Calcium / metabolism
  • Endoplasmic Reticulum / chemistry
  • Endoplasmic Reticulum / metabolism*
  • Humans
  • Mitochondria / chemistry
  • Mitochondria / metabolism*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction*


  • Reactive Oxygen Species
  • Calcium