The Interface Between ER and Mitochondria: Molecular Compositions and Functions

Abstract

Mitochondria and endoplasmic reticulum (ER) are essential organelles in eukaryotic cells, which play key roles in various biological pathways. Mitochondria are responsible for ATP production, maintenance of Ca²⁺ homeostasis and regulation of apoptosis, while ER is involved in protein folding, lipid metabolism as well as Ca²⁺ homeostasis. These organelles have their own functions, but they also communicate via mitochondrial-associated ER membrane (MAM) to provide another level of regulations in energy production, lipid process, Ca²⁺ buffering, and apoptosis. Hence, defects in MAM alter cell survival and death. Here, we review components forming the molecular junctions of MAM and how MAM regulates cellular functions. Furthermore, we discuss the effects of impaired ER-mitochondrial communication in various neurodegenerative diseases.

Keywords: ER-mitochondria tethering; mitochondrial-associated ER membrane (MAM); neurodegenerative disease.

Fig 1. Composition of ER-mitochondria interface

Yeast-specific ERMES is composed by a multiprotein complex including ER protein Mmm1, cytosolic protein Mdm12, as well as mitochondrial protein Mdm34 and Mdm10. In mammalian cells, the interface between ER and mitochondria contains MFN2-MFN1/2, BAP31-Fis1, IP3R-Grp75-VDAC, and PTPIP51-VAPB or −ORP5/8 tethering complexes, which makes the two organelles close juxtaposition. Other single proteins, such as PS2, PACS-2, Tespa1, SigR1 and MCU, are also associated in the ER-mitochondria tethering complexes.