Nuclear lipid droplets – how are they different from their cytoplasmic siblings?

Abstract

Lipid droplets (LDs) in the cytoplasm are formed in the endoplasmic reticulum (ER) and are connected with various organelles, both structurally and functionally. This is in contrast to LDs in the nucleus, which are separated from organelles in the cytoplasm. How nuclear lipid droplets form and what function they have were not known for many years. Recent results have revealed that nuclear LDs in hepatocytes are derived from lipoprotein precursors in the ER lumen, whereas those in non-hepatocytes and budding yeast newly form in the inner nuclear membrane. Although nuclear LDs are far fewer in number than cytoplasmic LDs, the unique location appears to bestow upon them specific functions, which are potentially linked to nuclear biology. This Review will provide an overview of our current understanding of nuclear LDs, discuss how they are different from cytoplasmic LDs and highlight knowledge gaps that need to be filled in future studies.

SIR telomere silencing depends on nuclear envelope lipids and modulates sensitivity to a lysolipid

“…CCT represents the rate limiting and committed step for the synthesis of PC through the Kennedy pathway, and edelfosine alters its recruitment to membranes while inhibiting the pathway in both yeast and mammalian cells ( Boggs et al, 1995 ; Zaremberg and McMaster, 2002 ). Of note, it has been shown that in hepatocytes nLDs recruit CCTα ( Fujimoto, 2022 ; Sołtysik et al, 2019 ). Since we show herein that edelfosine induces nLD biogenesis ( Fig.…”

The lipid droplet lipidome

“…For nLDs derived by budding from the inner nuclear membrane, metabolic interplay between PA and DG lipids was proposed [71]. In hepatocytes, nLDs are believed to derive from ER luminal LDs, which are triggered by ER stress and translocate into the nucleus via the type I nucleoplasmic reticulum [72,73]. Little is known so far about the lipidome composition of luminal LDs, but it was demonstrated that, in comparison to cytoplasmic LDs with a TG/PL ratio of 80 to 20 mol%, luminal LDs contained much less TG and an almost equal fraction of PLs [58].…”

The Janus-Faced Role of Lipid Droplets in Aging: Insights from the Cellular Perspective

“…Referring to the presence of Ces1d in nLDs in Drosophila , carboxylesterases may also participate in nLD biogenesis. In mammalian cells, nLDs are formed either de novo at the inner nuclear membrane or upon translocation of cytosolic LDs, originating from ER resident lipoprotein precursors, to the nucleoplasmic reticulum terminally moving to the nucleoplasm (recently reviewed by Fujimoto [ 265 ]). In hepatocytes, ER stress promotes LD shuttling to the nucleus and requires the activity of promyelocytic leukemia protein (PML) locating to the inner nuclear membrane.…”

“…In hepatocytes, ER stress promotes LD shuttling to the nucleus and requires the activity of promyelocytic leukemia protein (PML) locating to the inner nuclear membrane. PML, which is critical to nuclear signaling, can be retained in nLDs (then termed lipid-associated PML structures; LAPS) and due to the PML binding properties, nLDs/LAPS may regulate the PML-mediated control of the gene- expression, for instance, as part of lipid stress responses [ 265 , 266 ]. The above-mentioned association between stress responses and nLDs in C. elegans (see Section 3 ) may point in a similar direction and it cannot be excluded that nLDs assist cytosolic LDs in directing the expression of lipid-metabolism-linked genes.…”