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

•Endoplasmic reticulum (ER)-mitochondria contacts modulate several cell functions.•Different proteins are involved in ER-mitochondria tethering formation/modulation.•Alterations in ER-mitochondria coupling have been observed in several diseases.

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.

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