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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.
Highlights
Lipid droplets (LDs) have been established as genuine organelles with a relevant role in the control of cellular stress and various diseases
LDs utilize the cytoskeleton and molecular motor proteins such as kinesin, dynein and myosin [13]. These movements on actin or microtubules are uni- or bidirectional, and ethanol-induced hyperacetylation of microtubules leads to LD immobility in a hepatoma derived cell line [14]
These observations may support the general view that malfunctions in the establishment of protein tethers and “lipid bridges” between LDs and a broad variety of organelles contribute to several disease states, especially neuronal diseases
Summary
LDs have been established as genuine organelles with a relevant role in the control of cellular stress and various diseases. LDs were considered to be inert “oil bodies” inside a cell, but have gained attention as organelles with a distinct proteome [1]. LDs originate from the endoplasmic reticulum (ER) and consist of a neutral lipid core, which is surrounded by a phospholipid monolayer [2]. LDs are storage organelles for lipids and contribute to energy homeostasis [6]. LDs physically attach to and connect different organelles including. Shuttled to mitochondria or peroxisomes, LDs directly donate fatty acids (FAs) for beta oxidation in mammals [8]. LDs are involved in the utilization and exchange of lipids and contribute to cellular protein transport and distribution [9]
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