Nuclear lipid droplets identified by electron microscopy of serial sections

Abstract

BackgroundRecent studies have suggested that nuclear lipid droplets (LDs) are organized into domains similar to those of cytoplasmic LDs. As cytoplasmic LDs are formed at the endoplasmic reticulum (ER) membrane, which is structurally continuous with the nuclear envelope, it could be suggested however that nuclear LDs are cytoplamic LDs trapped within an invagination of the nuclear envelope. The resolution of fluorescence confocal microscopy is not sufficiently high to exclude this hypothesis.FindingsWe therefore addressed this question by electron microscopy (EM) of serial sections. In human liver tissue, we observed some cytoplamic LDs partly surrounded by the nuclear compartment, but we were also able to identify LDs residing in the nuclear compartment that were not connected to the nuclear envelope.ConclusionThese findings indicate that nuclear LDs constitute specific subdomains of the nuclear compartment probably involved in nuclear lipid homeostasis.

Immunohistochemical staining of lipid droplets with adipophilin in paraffin-embedded glioma tissue identifies an association between lipid droplets and tumour grade

“…Nuclear lipid droplets were also detected within occasional neurons. Although most studies have focused on cytoplasmic lipid droplets [3,4], recent evidence using confocal and electron microscopy in cultured hepatocytes suggests that neutral lipids within the nucleus also form into spherical lipid droplets of unique composition and size and that these may be involved with nuclear lipid homeostasis [29,30]. Alternatively it has also been proposed that cytoplasmic lipid droplets may be mistaken as nuclear in instances where they have a close association with the nuclear envelope [31].…”

Molecular Mechanisms and Physiological Significance of Organelle Interactions and Cooperation

“…All the core autophagy machinery associated genes are necessary for yeast lipophagy except Shp1, Vps38, Nyv1, Atg11, and Atg20. Tubulin and Vac8, which is involved in multiple vacuolar processes, are also important (van Zutphen et al, 2014). Wang et al also reported that the existence of a sterol-enriched vacuolar microdomain is important for stationary phase yeast LDs translocation and hypothesized a feedforward loop to promote stationary phase lipophagy .…”

“…Isolated nLDs contained a higher ratio of free cholesterol and cholesteryl esters to triacylglycerols than cytoplasmic droplets. In an ultrastructural study of human livers taken at autopsy, most nLDs were observed as invaginations of the nuclear envelope, although the rare nLD (seen in about 1% of hepatocytes) was clearly separated from the envelope (Uzbekov and Roingeard, 2013). Nuclear droplets were also observed in yeast although only in cells with mutated or deleted seipin (Cartwright et al, 2015).…”

“…In contrast to mammalian cells, lipophagy in yeast more closely resembles microautophagy and requires steps to modify the vacuolar membrane for engulfment of LDs (van Zutphen et al, 2014;. All the core autophagy machinery associated genes are necessary for yeast lipophagy except Shp1, Vps38, Nyv1, Atg11, and Atg20.…”

“…Lipophagy, as an alternative to lipolysis by droplet or cytosolic lipases, has been reported in yeast, adipocytes, enterocytes, fibroblasts, neurons, and stellate cells (Singh et al, 2009b;Lettieri Barbato et al, 2013;Liu and Czaja, 2013;Khaldoun et al, 2014;van Zutphen et al, 2014;. It can involve autophagosome formation (macrolipophagy), direct interaction of droplet with lysosome (microlipophagy), or chaperone-mediated autophagy (CMA).…”