Friend or Foe: Lipid Droplets as Organelles for Protein and Lipid Storage in Cellular Stress Response, Aging and Disease

Abstract

Lipid droplets (LDs) were considered as a mere lipid storage organelle for a long time. Recent evidence suggests that LDs are in fact distinct and dynamic organelles with a specialized proteome and functions in many cellular roles. As such, LDs contribute to cellular signaling, protein and lipid homeostasis, metabolic diseases and inflammation. In line with the multitude of functions, LDs interact with many cellular organelles including mitochondria, peroxisomes, lysosomes, the endoplasmic reticulum and the nucleus. LDs are highly mobile and dynamic organelles and impaired motility disrupts the interaction with other organelles. The reduction of interorganelle contacts results in a multitude of pathophysiologies and frequently in neurodegenerative diseases. Contacts not only supply lipids for β-oxidation in mitochondria and peroxisomes, but also may include the transfer of toxic lipids as well as misfolded and harmful proteins to LDs. Furthermore, LDs assist in the removal of protein aggregates when severe proteotoxic stress overwhelms the proteasomal system. During imbalance of cellular lipid homeostasis, LDs also support cellular detoxification. Fine-tuning of LD function is of crucial importance and many diseases are associated with dysfunctional LDs. We summarize the current understanding of LDs and their interactions with organelles, providing a storage site for harmful proteins and lipids during cellular stress, aging inflammation and various disease states.

Loss of swiss cheese in Neurons Contributes to Neurodegeneration with Mitochondria Abnormalities, Reactive Oxygen Species Acceleration and Accumulation of Lipid Droplets in Drosophila Brain

“…LDs interact with many cellular organelles, including mitochondria, peroxisomes, lysosomes, the endoplasmic reticulum and the nucleus. In stress conditions, LDs have a supportive role, reducing mitochondrial and endoplasmic reticulum stress, protein or lipid toxicity effects [ 119 , 120 , 121 , 122 , 123 ]. LDs are abundant in various organs in animals, including the gut, fat tissue and the brain in Drosophila melanogaster [ 120 ].…”

Celia’s Encephalopathy (BSCL2-Gene-Related): Current Understanding

“…In particular, seipin in its toroidal formation would anchor the nascent LD around the bridge between ER and LD [ 22 ]. This, in association with other partners, favors the flow of lipids into the LD, thus promoting their growth, until they are separated from the ER in the cytoplasm [ 23 ]. However, the mechanism by which the latter occurs has not been elucidated to date.…”

A lipid droplet-peroxisome network drives longevity by monounsaturated fatty acids via modulating ether lipid synthesis and ferroptosis

“…Lipid droplets have also been found to act as innate immune hubs that can kill pathogens 92 . In contrast, lipid droplets also accumulate during old age and disease 93 and are detrimental in many contexts [25][26][27]31,33,[94][95][96] . Furthermore, conditions that lead to fat storage but also lipolysis have been associated with longevity 42,[97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113][114] .…”