A Unique Junctional Interface at Contact Sites Between the Endoplasmic Reticulum and Lipid Droplets

Abstract

Lipid droplets (LDs) constitute compartments dedicated to the storage of metabolic energy in the form of neutral lipids. LDs originate from the endoplasmic reticulum (ER) with which they maintain close contact throughout their life cycle. These ER–LD junctions facilitate the exchange of both proteins and lipids between these two compartments. In recent years, proteins that are important for the proper formation of LDs and localize to ER–LD junctions have been identified. This junction is unique as it is generally believed to invoke a transition from the ER bilayer membrane to a lipid monolayer that delineates LDs. Proper formation of this junction requires the ordered assembly of proteins and lipids at specialized ER subdomains. Without such a well-ordered assembly of LD biogenesis factors, neutral lipids are synthesized throughout the ER membrane, resulting in the formation of aberrant LDs. Such ectopically formed LDs impact ER and lipid homeostasis, resulting in different types of lipid storage diseases. In response to starvation, the ER–LD junction recruits factors that tether the vacuole to these junctions to facilitate LD degradation. In addition, LDs maintain close contacts with peroxisomes and mitochondria for metabolic channeling of the released fatty acids toward beta-oxidation. In this review, we discuss the function of different components that ensure proper functioning of LD contact sites, their role in lipogenesis and lipolysis, and their relation to lipid storage diseases.

Protein Aggregation in the ER: Calm behind the Storm

“…For example, muscle cells have a high content of smooth ER for calcium storage, while B cells and pancreatic acinar cells contain predominantly rough ER for generating secretory proteins [ 6 ]. Moreover, the ER keeps in close contact with many other organelles, such as mitochondria, lysosomes, lipid droplets, and Golgi via membrane contact sites, which in turn modulate lipid metabolism, calcium signaling, energy production, protein degradation, and other cellular activities [ 7 , 8 , 9 ]. Hence, the ER is a central player in the regulation of physiological processes of eukaryotic cells.…”

Endoplasmic Reticulum Stress in Diabetic Nephrology: Regulation, Pathological Role, and Therapeutic Potential

“…The ER is an important subcellular organ in eukaryotic cells. It facilitates the synthesis and export of proteins and lipids [ 4 ]. It can fold proteins in the cisternae and transport synthesized proteins to the Golgi apparatus through vesicles.…”

The surface of lipid droplets constitutes a barrier for endoplasmic reticulum-resident integral membrane proteins

“…at sites of contact between the ER and LDs) or whether it is the hemimembrane itself that prevents the repositioning of these membrane proteins from a bilayer membrane onto the monolayer remains an open question. The interface between the ER bilayer and the LD monolayer is constituted by both a seipin oligomeric ring and FIT proteins, and is likely to contain additional factors such as LD-associated factor (LDAF1, also known as promethin) and lipid-modifying enzymes such as acyltransferases (Lro1) or the phosphatidate phosphatase (Pah1) and its regulators (Nem1-Spo7) (Choudhary et al, 2018(Choudhary et al, , 2020Choudhary and Schneiter, 2021;Chung et al, 2019;Salo et al, 2019;Yan et al, 2018). Whether and how hairpin-containing membrane proteins can pass through this protein interface or whether they are directly inserted into the limiting membrane of LDs remains to be established (Schrul and Kopito, 2016).…”