The endoplasmic reticulum-mitochondria coupling in health and disease: Molecules, functions and significance

Abstract

The close apposition between endoplasmic reticulum (ER) and mitochondria represents a key platform, capable to regulate different fundamental cellular pathways. Among these, Ca²⁺ signaling and lipid homeostasis have been demonstrated over the last years to be deeply modulated by ER-mitochondria cross-talk. Given its importance in cell life/death decisions, increasing evidence suggests that alterations of the ER-mitochondria axis could be responsible for the onset and progression of several diseases, including neurodegeneration, cancer and obesity. However, the molecular identity of the proteins controlling this inter-organelle apposition is still debated. In this review, we summarize the main cellular pathways controlled by ER-mitochondria appositions, focusing on the principal molecules reported to be involved in this interplay and on those diseases for which alterations in organelles communication have been reported.

Keywords: Calcium (Ca(2+)); ER-mitochondria tethering; Endoplasmic reticulum (ER); Inter-organelle contacts; Mitochondria; Mitochondria-Associated Membranes (MAMs); Mitofusin 2.