Mitochondria-associated niches in health and disease.

The appreciation of the importance of interorganelle contacts has steadily increased over the past decades. Advances in imaging, molecular biology and bioinformatic techniques allowed the discovery of new mechanisms involved in the interaction and communication between organelles, providing novel insights into the inner works of a cell. In this Review, with the mitochondria under the spotlight, we discuss the most recent findings on the mechanisms mediating the communication between organelles, focusing on Ca2+ signaling, lipid exchange, cell death and stress responses. Notably, we introduce a new integrative perspective to signaling networks that is regulated by interorganelle interactions - the mitochondria-associated niches - focusing on the link between the molecular determinants of contact sites and their functional outputs, rather than simply physical and structural communication. In addition, we highlight the neuropathological and metabolic implications of alterations in mitochondria-associated niches and outline how this concept might improve our understanding of multi-organelle interactions.