Dysregulation of organelle membrane contact sites in neurological diseases

The defining evolutionary feature of eukaryotic cells is the emergence of membrane-bound organelles. Compartmentalization allows each organelle to maintain a spatially, physically, and chemically distinct environment, which greatly bolsters individual organelle function. However, the activities of each organelle must be balanced and are interdependent for cellular homeostasis. Therefore, properly regulated interactions between organelles, either physically or functionally, remain critical for overall cellular health and behavior. In particular, neuronal homeostasis depends heavily on the proper regulation of organelle function and cross talk, and deficits in these functions are frequently associated with diseases. In this review, we examine the emerging role of organelle contacts in neurological diseases and discuss how the disruption of contacts contributes to disease pathogenesis. Understanding the molecular mechanisms underlying the formation and regulation of organelle contacts will broaden our knowledge of their role in health and disease, laying the groundwork for the development of new therapies targeting interorganelle cross talk and function.