Lipid droplets (LDs) are evolutionarily conserved intracellular organelles that play pivotal roles in regulating cellular lipid homeostasis, energy metabolism, and numerous biological processes. Dysfunction of LD dynamic is closely associated with a spectrum of human disorders, especially metabolic diseases, including obesity, type 2 diabetes, cardiovascular diseases, and metabolic dysfunction-associated steatotic liver disease. Long regarded as passive lipid storage organelles, LDs are now recognized as dynamic and multifunctional cellular hubs with rapidly new technological advances in the last two decades.
This review systematically summarizes the current advances and understanding of LD biology, focusing on the life cycle of LDs, covering biogenesis, growth, fusion, fission, and degradation. Distinct from cytoplasmic LDs, the biogenesis and unique characteristics of nuclear-derived LDs are also discussed. Meanwhile, this review also clarifies the structural and functional diversity and heterogeneity of LDs across cells, tissues, and organisms. Furthermore, this review summarizes four major protein targeting pathways, and also highlights the extensive physical and functional interactions between LDs and other organelles that coordinate cellular metabolism and stress adaptation. Moreover, LDs in the brain, such as neurons and glial cells, play a dual role under both physiological and pathological conditions, which may reshape our thoughts regarding the pathogenesis of neuronal diseases.
Advanced research technologies for LD study, including proximity labeling proteomic approaches and novel fluorescent probes, are also included and discussed. In the end, several key open questions are provided for potential directions for future LD research. In summary, this review hopefully provides a systematic and insightful reference for LD biology exploration and their pathological implications.
DOI：10.1093/procel/pwag048