Abstract
Cells prepare for fluctuations in nutrient availability by storing energy in the form of neutral lipids in organelles called Lipid Droplets (LDs). Upon starvation, fatty acids (FAs) released from LDs are trafficked to different cellular compartments to be utilized for membrane biogenesis or as a source of energy. Despite the biochemical pathways being known in detail, the spatio-temporal regulation of FA synthesis, storage, release, and breakdown is not completely understood. Recent studies suggest that FA trafficking and metabolism are facilitated by inter-organelle contact sites that form between LDs and other cellular compartments such as the Endoplasmic Reticulum (ER), mitochondria, peroxisomes, and lysosomes. LD-LD contact sites are also sites where FAs are transferred in a directional manner to support LD growth and expansion. As the storage site of neutral lipids, LDs play a central role in FA homeostasis. In this mini review, we highlight the role of LD contact sites with other organelles in FA trafficking, channeling, and metabolism and discuss the implications for these pathways on cellular lipid and energy homeostasis.
Highlights
Maintaining energy homeostasis is obligatory for cellular survival and fitness
Stored fatty acids (FAs) can be released under stress conditions or when nutrients are limited, in order to be used for the synthesis of membrane lipids or to fuel energy production
These neutral lipids are incapable of forming membranes; they are sequestered in specific organelles known as Lipid Droplets (LDs) that form at the Endoplasmic Reticulum (ER) (Fujimoto and Ohsaki, 2006; Walther et al, 2017; Olzmann and Carvalho, 2019)
Summary
Maintaining energy homeostasis is obligatory for cellular survival and fitness. In general, cells store energy in the form of fatty acids (FAs) when nutrients are abundant or in excess. As many processes involved in energy and lipid metabolism are not localized to LDs, close collaboration and communication with other organelles is required To this extent, LDs form contact sites with various organelles (Gao and Goodman, 2015; Schuldiner and Bohnert, 2017; Figure 1). Several proteins have been reported to reside and function at LD-organelle contact sites possibly functioning in the formation of neutral lipid metabolon to locally regulate FA metabolism (Henne et al, 2020). These proteins include lipid-transfer proteins and FA-modifying enzymes suggesting that LD-organelle sites are specialized cellular locales where FA metabolism is compartmentalized. We discuss the implications of this organization on cellular metabolism and lipid homeostasis
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