The very-long-chain fatty acid elongase Elo2 rescues lethal defects associated with loss of the nuclear barrier function in fission yeast cells

Y Kinugasa, Y Hirano, M Sawai, Y Ohno… - Journal of cell …, 2019 - journals.biologists.com
Y Kinugasa, Y Hirano, M Sawai, Y Ohno, T Shindo, H Asakawa, Y Chikashige, S Shibata
Journal of cell science, 2019journals.biologists.com
In eukaryotic cells, chromosomes are confined to the nucleus, which is compartmentalized
by the nuclear membranes; these are continuous with the endoplasmic reticulum
membranes. Maintaining the homeostasis of these membranes is an important cellular
activity performed by lipid metabolic enzymes. However, how lipid metabolic enzymes affect
nuclear membrane functions remains to be elucidated. We found that the very-long-chain
fatty acid elongase Elo2 is located in the nuclear membrane and prevents lethal defects …
Abstract
In eukaryotic cells, chromosomes are confined to the nucleus, which is compartmentalized by the nuclear membranes; these are continuous with the endoplasmic reticulum membranes. Maintaining the homeostasis of these membranes is an important cellular activity performed by lipid metabolic enzymes. However, how lipid metabolic enzymes affect nuclear membrane functions remains to be elucidated. We found that the very-long-chain fatty acid elongase Elo2 is located in the nuclear membrane and prevents lethal defects associated with nuclear membrane ruptures in mutants of the nuclear membrane proteins Lem2 and Bqt4 in the fission yeast Schizosaccharomyces pombe. Lipid composition analysis shows that t20:0/24:0 phytoceramide (a conjugate of C20:0 phytosphingosine and C24:0 fatty acid) is a major ceramide species in S. pombe. The quantity of this ceramide is reduced in the absence of Lem2, and restored by increased expression of Elo2. Furthermore, loss of S. pombe Elo2 can be rescued by its human orthologs. These results suggest that the conserved very-long-chain fatty acid elongase producing the ceramide component is essential for nuclear membrane integrity and cell viability in eukaryotes.
This article has an associated First Person interview with the first author of the paper.
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