The interplay of lipid droplets, mitochondria, and ER in governing hepatic lipid metabolism

Lipid metabolism and storage are highly compartmentalized processes. Key organelles defined to govern lipid synthesis (ER), storage (lipid droplets, LDs), and catabolism (mitochondria) work in synchrony to coordinate lipid metabolic flux. Interactions between these organelles play important roles in metabolite exchange and signaling that vary in response to physiological conditions. Alterations in organelle crosstalk or imbalances between anabolic and catabolic pathways are commonly observed in diseased states, including metabolic dysfunction-associated steatotic liver disease (MASLD). While many studies have characterized two-organelle interactions (e.g., LD mitochondria), there is a general lack of consideration of how the presence of other organelles impacts the function of these contacts. This review aims to provide a concise summary of the regulation, function, and complexity of how these organelle interactions compartmentalize hepatic lipid metabolism.