Abstract
Lipid droplets (LDs) have emerged not just as storage sites for lipids but as central regulators of metabolism and organelle quality control. These critical functions are achieved, in part, at membrane contact sites (MCS) between LDs and other organelles. MCS are sites of transfer of cellular constituents to or from LDs for energy mobilization in response to nutrient limitations, as well as LD biogenesis, expansion and autophagy. Here, we describe recent findings on the mechanisms underlying the formation and function of MCS between LDs and mitochondria, ER and lysosomes/vacuoles and the role of the cytoskeleton in promoting LD MCS through its function in LD movement and distribution in response to environmental cues.
Highlights
Lipid droplets (LDs) have an established function in storing lipids, which are used for energy production, membrane biogenesis and synthesis of signaling molecules
membrane contact sites (MCS) that form between LDs and organelles including mitochondria, endoplasmic reticulum (ER) and lysosomes/vacuoles function in LD biogenesis and in transfer of lipids, Fatty acids (FAs), unfolded proteins and surplus or toxic proteins to or from LDs
Emerging evidence supports a role for the cytoskeleton in formation of MCS between LDs and other organelles by controlling the position and movement of LDs in response to environmental cues
Summary
Lipid droplets (LDs) have an established function in storing lipids, which are used for energy production, membrane biogenesis and synthesis of signaling molecules. Proteins are associated with LDs, conventional transport proteins that are integrated into lipid bilayers do not take part in transfer of lipids and other constituents from LDs to other organelles. Instead, specialized proteins, such as lipases that associate with the LD boundary membrane, release lipids and vitamin A from LDs (Schreiber et al, 2012; O’Byrne and Blaner, 2013; Grumet et al, 2016; Olzmann and Carvalho, 2019). Toxic lipids or proteins that are sequestered in LDs can be delivered to lysosomes (the vacuole in yeast) by multiple pathways, including transfer events at LD-lysosome contact sites and piecemeal or wholesale uptake of LDs into the lysosome/vacuolar compartment (Tsuji et al, 2017; Schulze et al, 2020; Garcia et al, 2021; Liao et al, 2021). We review recent findings on the structure and function of LD MCS in yeast and mammalian cells, and how these membrane contacts respond to cellular or environmental cues
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