Alterations in Ca²⁺ Signalling via ER-Mitochondria Contact Site Remodelling in Cancer

Inter-organellar contact sites establish microdomains for localised Ca²⁺-signalling events. One of these microdomains is established between the ER and the mitochondria. Importantly, the so-called mitochondria-associated ER membranes (MAMs) contain, besides structural proteins and proteins involved in lipid exchange, several Ca²⁺-transport systems, mediating efficient Ca²⁺ transfer from the ER to the mitochondria. These Ca²⁺ signals critically control several mitochondrial functions, thereby impacting cell metabolism, cell death and survival, proliferation and migration. Hence, the MAMs have emerged as critical signalling hubs in physiology, while their dysregulation is an important factor that drives or at least contributes to oncogenesis and tumour progression. In this book chapter, we will provide an overview of the role of the MAMs in cell function and how alterations in the MAM composition contribute to oncogenic features and behaviours.