Remodelling of mitochondrial function by import of specific lipids at multiple membrane-contact sites

Organelles form physical and functional contact between each other to exchange information, metabolic intermediates, and signaling molecules. Tethering factors and contact site complexes bring partnering organelles into close spatial proximity to establish membrane contact sites (MCSs), which specialize in unique functions like lipid transport or Ca2+ signaling. Here, we discuss how MCSs form dynamic platforms that are important for lipid metabolism. We provide a perspective on how import of specific lipids from the ER and other organelles may contribute to remodeling of mitochondria during nutrient starvation. We speculate that mitochondrial adaptation is achieved by connecting several compartments into a highly dynamic organelle network. The lipid droplet appears to be a central hub in coordinating the function of these organelle neighborhoods. Metabolic homeostasis depends on the functional remodeling of organelles. During starvation, this is especially evident for mitochondria. In this perspective, we outline a possible mechanism by which lipid transport at membrane contact sites might control the adaptation of mitochondrial activities. We conclude with the notion that mitochondria interact with a whole network of organelles to achieve this important physiological task. image