Lipid droplet functions beyond energy storage

Abstract

Lipid droplets are cytoplasmic organelles that store neutral lipids and are critically important for energy metabolism. Their function in energy storage is firmly established and increasingly well characterized. However, emerging evidence indicates that lipid droplets also play important and diverse roles in the cellular handling of lipids and proteins that may not be directly related to energy homeostasis. Lipid handling roles of droplets include the storage of hydrophobic vitamin and signaling precursors, and the management of endoplasmic reticulum and oxidative stress. Roles of lipid droplets in protein handling encompass functions in the maturation, storage, and turnover of cellular and viral polypeptides. Other potential roles of lipid droplets may be connected with their intracellular motility and, in some cases, their nuclear localization. This diversity highlights that lipid droplets are very adaptable organelles, performing different functions in different biological contexts. This article is part of a Special Issue entitled: Recent Advances in Lipid Droplet Biology edited by Rosalind Coleman and Matthijs Hesselink.

Keywords: ER stress; Lipid droplet; Motility; Sequestration.

Figure 1. Lipid droplets protect against ROS damage in the neural stem cell niche of Drosophila

Left: During Drosophila CNS development, neural stem cells (neuroblasts) divide to generate daughter cells that will give rise to neurons. Adjacent glia constitute the neural stem cell niche, a microenvironment that promotes neuroblast divisions. Right: Magnified view of glia and neuroblast membranes. Neuroblasts are able to sustain their divisions during normoxia or during hypoxia if adjacent glia can synthesize triglycerides stored in lipid droplets. During hypoxia without glial lipid droplets, ROS accumulate and induce the peroxidation of membrane lipids containing PUFAs (green) leading to their damage (red). In the case of the PUFA linoleic acid, this gives rise to a reactive aldehyde (4-hydroxynonenal, 4-HNE), which forms damaging adducts with macromolecules. 4-HNE also triggers more ROS, resulting in an escalating feedback loop. The accumulating damage then inhibits neuroblast divisions. During hypoxia with glial lipid droplets, a proportion of the total membrane fatty acids (including those containing PUFAs) are diverted into lipid droplets where they are protected from ROS-induced damage and thus from triggering the feedback loop between ROS and 4-HNE. This antioxidant role of lipid droplets helps to minimize cellular damage during hypoxia, enabling neuroblasts to continue dividing. Reprinted from Cell, Vol. 163, Michael A. Welte, How brain fat conquers stress, pp. 269-270, Copyright (2015) [232], with permission from Elsevier.

Figure 2. Potential intersection between lipid and protein homeostasis

Droplet number per cell might modulate the effective concentration of associated proteins: Too many droplets (right) might tie up too much of the protein. Too few droplets (left) might allow a toxic protein to reach a free concentration that is detrimental.