The ER-mitochondria tether at the hub of Ca2+ signaling

Inter-organelle contacts are emerging as crucial hubs in cell signaling. Among these, the long known ER-mitochondria tethers can be considered a reference model for these communication structures. Here, signal crosstalk at the interface of ER and mitochondria occurs thanks to lipids exchange and Ca2+ flux across these specialized structures. How this signal is modulated depends on the compositions of the proteins that are engaged at these areas of membrane proximity. These proteins modulate the activity of Ca2+ channels and regulate contact structure remodeling in response to cellular cues. In this review, we highlight the molecular aspects of the ER-mitochondria contacts and how they impact on Ca2+ signaling and thus on cell physiology.