Lipid droplet autophagy during energy mobilization lipid homeostasis and protein quality control

Abstract

Lipid droplets (LDs) have well-established functions as sites for lipid storage and energy mobilization to meet the metabolic demands of cells. However, recent studies have expanded the roles of LDs to protein quality control. Lipophagy, or LD degradation by autophagy, plays a vital role not only in the mobilization of free fatty acids (FFAs) and lipid homeostasis at LDs, but also in the adaptation of cells to certain forms of stress including lipid imbalance. Recent studies have provided new mechanistic insights about the diverse types of lipophagy, in particular microlipophagy. This review summarizes key findings about the mechanisms and functions of lipophagy and highlights a novel function of LD microlipophagy as a mechanism to maintain endoplasmic reticulum (ER) proteostasis under conditions of lipid imbalance.

Lipid Droplets in Cancer: Guardians of Fat in a Stressful World

“…CMA is a specialized form of selective autophagy, so far characterized only in mammalian cells, and includes a motif-based recognition of damaged proteins by the heat shock cognate protein of 70 kDa (Hsc70) and lysosomal intake mediated by the lysosome-associated membrane protein type 2 (LAMP-2A) [ 236 ]. In contrast, microautophagy enables the uptake of cytoplasmic material by a direct invagination of the lysosomal membrane and it has been characterized in yeast [ 46 , 237 ], while its importance in mammalian cells is still questionable.…”

“…A sudden depletion of glucose in yeast cells activates AMPK-dependent lipid droplet breakdown by microautophagy, i.e., microlipophagy, and provides energy for long-term survival [ 258 ]. Microlipophagy has also been implicated in the management of ER lipid and protein quality control during phospholipid imbalance-induced ER stress [ 46 , 237 ]. It was found that lipid droplets are formed at ER aggregates and act as carriers for the transfer of damaged proteins and toxic lipids from the ER to the vacuole through microlipophagy [ 46 , 237 ].…”

“…Microlipophagy has also been implicated in the management of ER lipid and protein quality control during phospholipid imbalance-induced ER stress [ 46 , 237 ]. It was found that lipid droplets are formed at ER aggregates and act as carriers for the transfer of damaged proteins and toxic lipids from the ER to the vacuole through microlipophagy [ 46 , 237 ]. Whether microautophagy occurs in mammalian cells is still unknown, but an alternative pathway of endosomal autophagy shares similar characteristics [ 259 ] and has a physiological role in erythropoiesis in vivo [ 260 ].…”

“…Fourth, lipid droplets are crucial for the maintenance of membrane and ER homeostasis. They contribute to membrane and protein quality control and are involved in the removal of damaged lipids, aggregated and unfolded proteins, thereby reducing ER stress [ 16 , 19 , 26 , 40 , 45 , 46 , 47 ]. Emerging studies suggest that alterations in lipid droplet breakdown through lipolysis and autophagy have a profound effect on the management of membrane and ER homeostasis, oxidative stress, mitochondrial function, and stress signalling (see Section 5 , Section 7 and Section 8 ) [ 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ].…”

The Impact of ESCRT on Aβ1-42 Induced Membrane Lesions in a Yeast Model for Alzheimer’s Disease

“…The cryo-EM study also pointed to the formation of cortical vesicle-like structures, which we believe may correspond to lipid droplets. Since previous studies have shown that the formation of lipid droplets denotes an adaptive response to a chronic lipid imbalance ( Vevea et al, 2015 ; Garcia et al, 2018 ), which is likely to occur in bro1Δ strain because of hampered MVB formation and lipid turnover, we decided to perform a Nile Red staining to visualize the droplets. While during the first hours of induction on galactose-containing medium we observed an overall enhanced lipid droplet biogenesis in all bro1 Δ strains as compared to the respective wild-type strains, the increase was persistent and especially more dense droplets were seen with bro1 Δ cells expressing αAβ 42 G37C or αAβ 42 wt (Figure 6A ).…”