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Article ; Online: Oiling the wheels of nuclear division: SUMOylation regulates the expansion of the mitotic nuclear membrane.

Siniossoglou, Symeon

2023 Volume 222, Issue 8

Abstract: Eukaryotic cell division involves the segregation of chromosomes between two daughter cells and must be coordinated with extensive rearrangement of their nuclear envelopes. In this issue, Saik et al. (2023 J. Cell Biol. https://doi.org/10.1083/jcb ... ...

Abstract	Eukaryotic cell division involves the segregation of chromosomes between two daughter cells and must be coordinated with extensive rearrangement of their nuclear envelopes. In this issue, Saik et al. (2023 J. Cell Biol. https://doi.org/10.1083/jcb.202208137) show that a SUMOylation cascade at the inner nuclear membrane elevates the levels of phosphatidic acid, a key phospholipid precursor, to support the need for nuclear membrane expansion during mitosis.
MeSH term(s)	Chromosomes ; Mitosis ; Nuclear Envelope/genetics ; Sumoylation ; Phosphatidic Acids
Chemical Substances	Phosphatidic Acids
Language	English
Publishing date	2023-07-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
DOI	10.1083/jcb.202306126
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Article ; Online: Membranes that make fat: roles of membrane lipids as acyl donors for triglyceride synthesis and organelle function.

Barbosa, Antonio D / Siniossoglou, Symeon

FEBS letters

2023

Abstract: Triglycerides constitute an inert storage form for fatty acids deposited in lipid droplets and are mobilized to provide metabolic energy or membrane building blocks. The biosynthesis of triglycerides is highly conserved within eukaryotes and normally ... ...

Abstract	Triglycerides constitute an inert storage form for fatty acids deposited in lipid droplets and are mobilized to provide metabolic energy or membrane building blocks. The biosynthesis of triglycerides is highly conserved within eukaryotes and normally involves the sequential esterification of activated fatty acids with a glycerol backbone. Some eukaryotes, however, can also use cellular membrane lipids as direct fatty acid donors for triglyceride synthesis. The biological significance of a pathway that generates triglycerides at the expense of organelle membranes has remained elusive. Here we review current knowledge on how cells use membrane lipids as fatty acid donors for triglyceride synthesis and discuss the hypothesis that a primary function of this pathway is to regulate membrane lipid remodeling and organelle function.
Language	English
Publishing date	2023-12-23
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	212746-5
ISSN	1873-3468 ; 0014-5793
ISSN (online)	1873-3468
ISSN	0014-5793
DOI	10.1002/1873-3468.14793
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Article ; Online: Nuclear Shape-Shifters: Lipid and Protein Dynamics at the Nuclear Envelope.

Antonin, Wolfram / Siniossoglou, Symeon

Cells

2022 Volume 11, Issue 24

Abstract: The nuclear envelope constitutes a selective barrier that segregates chromatin into the nucleus of eukaryotic cells [ ... ]. ...

Abstract	The nuclear envelope constitutes a selective barrier that segregates chromatin into the nucleus of eukaryotic cells [...].
Language	English
Publishing date	2022-12-19
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11244120
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Article ; Online: New kid on the block: lipid droplets in the nucleus.

Barbosa, Antonio D / Siniossoglou, Symeon

The FEBS journal

2020 Volume 287, Issue 22, Page(s) 4838–4843

Abstract: The regulation of lipid homeostasis is essential for normal cell physiology, and its disruption can lead to disease. Lipid droplets (LDs) are ubiquitous organelles dedicated to storing nonpolar lipids that are used for metabolic energy production or ... ...

Abstract	The regulation of lipid homeostasis is essential for normal cell physiology, and its disruption can lead to disease. Lipid droplets (LDs) are ubiquitous organelles dedicated to storing nonpolar lipids that are used for metabolic energy production or membrane biogenesis. LDs normally emerge from, and associate with, the endoplasmic reticulum and interact with other cytoplasmic organelles to deliver the stored lipids. Recently, LDs were found to reside also at the inner side of the nuclear envelope and inside the nucleus in yeast and mammalian cells. This unexpected finding raises fundamental questions about the nature of the inner nuclear membrane, its connection with the endoplasmic reticulum and the pathways of LD formation. In this viewpoint, we will highlight recent developments relating to these questions and discuss possible roles of LDs in nuclear physiology.
MeSH term(s)	Animals ; Cell Nucleus/metabolism ; Endoplasmic Reticulum/metabolism ; Homeostasis ; Humans ; Lipid Droplets/metabolism ; Lipid Metabolism ; Models, Biological ; Nuclear Envelope/metabolism ; Saccharomyces cerevisiae/metabolism
Language	English
Publishing date	2020-04-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.15307
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Article: Phospholipid metabolism and nuclear function: roles of the lipin family of phosphatidic acid phosphatases.

Siniossoglou, Symeon

Biochimica et biophysica acta

2012 Volume 1831, Issue 3, Page(s) 575–581

Abstract: Phospholipids play important roles in nuclear function as dynamic building blocks for the biogenesis of the nuclear membrane, as well as signals by which the nucleus communicates with other organelles, and regulate a variety of nuclear events. The ... ...

Abstract	Phospholipids play important roles in nuclear function as dynamic building blocks for the biogenesis of the nuclear membrane, as well as signals by which the nucleus communicates with other organelles, and regulate a variety of nuclear events. The mechanisms underlying the nuclear roles of phospholipids remain poorly understood. Lipins represent a family of phosphatidic acid (PA) phosphatases that are conserved from yeasts to humans and perform essential functions in lipid metabolism. Several studies have identified key roles for lipins and their regulators in nuclear envelope organization, gene expression and the maintenance of lipid homeostasis in yeast and metazoans. This review discusses recent advances in understanding the roles of lipins in nuclear structure and function. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism.
MeSH term(s)	Active Transport, Cell Nucleus/physiology ; Animals ; Cell Nucleus/metabolism ; Gene Expression Regulation ; Humans ; Isoenzymes/genetics ; Isoenzymes/metabolism ; Lipid Metabolism ; Nuclear Envelope/metabolism ; Phosphatidate Phosphatase/genetics ; Phosphatidate Phosphatase/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism
Chemical Substances	Isoenzymes ; Phosphatidate Phosphatase (EC 3.1.3.4)
Language	English
Publishing date	2012-09-29
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbalip.2012.09.014
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Article: Function of lipid droplet-organelle interactions in lipid homeostasis.

Barbosa, Antonio Daniel / Siniossoglou, Symeon

Biochimica et biophysica acta. Molecular cell research

2017 Volume 1864, Issue 9, Page(s) 1459–1468

Abstract: Storage of non-polar lipids in ubiquitous eukaryotic organelles, lipid droplets (LDs), prevents the toxic consequences of unesterified fatty acids and provides a lipid reservoir that can be promptly used to satisfy cellular needs under multiple metabolic ...

Abstract	Storage of non-polar lipids in ubiquitous eukaryotic organelles, lipid droplets (LDs), prevents the toxic consequences of unesterified fatty acids and provides a lipid reservoir that can be promptly used to satisfy cellular needs under multiple metabolic and physiological conditions. Tight temporal and spatial control of LD biogenesis and mobilization of neutral lipids is essential for the correct channelling of lipid intermediates to their various cellular destinations and the maintenance of cellular homeostasis. These functions are mediated by multiple interactions between LDs and other intracellular organelles that are required for the delivery of stored lipids. Here we review recent advances in the interactions of LDs with the endoplasmic reticulum (ER), mitochondria and vacuole/lysosome. This article is part of a Special Issue entitled: Membrane Contact Sites edited by Christian Ungermann and Benoit Kornmann.
MeSH term(s)	Animals ; Homeostasis ; Humans ; Intracellular Membranes/metabolism ; Lipid Droplet Associated Proteins/genetics ; Lipid Droplet Associated Proteins/metabolism ; Lipid Droplets/metabolism ; Lipid Metabolism
Chemical Substances	Lipid Droplet Associated Proteins
Language	English
Publishing date	2017-04-05
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0167-4889 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0167-4889 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbamcr.2017.04.001
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Article ; Online: Lipins, lipids and nuclear envelope structure.

Siniossoglou, Symeon

Traffic (Copenhagen, Denmark)

2009 Volume 10, Issue 9, Page(s) 1181–1187

Abstract: The lipid composition of biological membranes is crucial for many aspects of organelle function, including growth, signalling, and transport. Lipins represent a novel family of lipid phosphatases that dephosphorylate phosphatidic acid (PA) to produce ... ...

Abstract	The lipid composition of biological membranes is crucial for many aspects of organelle function, including growth, signalling, and transport. Lipins represent a novel family of lipid phosphatases that dephosphorylate phosphatidic acid (PA) to produce diacylglycerol (DAG), and perform key functions in phospholipid and triacylglycerol biosynthesis and gene expression. In addition to its role in lipid biosynthesis, the yeast lipin Pah1p and its regulators are required for the maintenance of a spherical nuclear shape. This review summarizes recent advances in our understanding of the yeast lipin Pah1p and highlights the possible roles of phospholipid metabolism in nuclear membrane biogenesis.
MeSH term(s)	Animals ; Lipid Metabolism ; Membrane Lipids/biosynthesis ; Membrane Lipids/metabolism ; Nuclear Envelope/metabolism ; Nuclear Envelope/ultrastructure ; Nuclear Proteins/biosynthesis ; Nuclear Proteins/metabolism ; Phosphatidate Phosphatase/biosynthesis ; Phosphatidate Phosphatase/metabolism ; Saccharomyces cerevisiae Proteins/biosynthesis ; Saccharomyces cerevisiae Proteins/metabolism
Chemical Substances	Membrane Lipids ; Nuclear Proteins ; Saccharomyces cerevisiae Proteins ; PAH1 protein, S cerevisiae (EC 3.1.3.4) ; Phosphatidate Phosphatase (EC 3.1.3.4)
Language	English
Publishing date	2009-05-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1483852-7
ISSN	1600-0854 ; 1398-9219
ISSN (online)	1600-0854
ISSN	1398-9219
DOI	10.1111/j.1600-0854.2009.00923.x
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Article: Spatial distribution of lipid droplets during starvation: Implications for lipophagy.

Barbosa, Antonio Daniel / Siniossoglou, Symeon

Communicative & integrative biology

2016 Volume 9, Issue 4, Page(s) e1183854

Abstract: Survival during starvation depends largely on metabolic energy, which is stored in the form of neutral lipids in specialized organelles known as lipid droplets. The precursors for the synthesis of neutral lipids are also used for membrane biogenesis, ... ...

Abstract	Survival during starvation depends largely on metabolic energy, which is stored in the form of neutral lipids in specialized organelles known as lipid droplets. The precursors for the synthesis of neutral lipids are also used for membrane biogenesis, which is required for cell growth and proliferation. Therefore cells must possess mechanisms to preferentially channel lipid precursors toward either membrane synthesis or lipid droplet storage, in response to nutrient status. How this partitioning is spatially regulated within the endoplasmic reticulum (ER) where lipid droplets co-localize, remains poorly understood. We have recently shown that at the onset of starvation lipid droplets concentrate at a perinuclear ER subdomain flanking the nucleus-vacuole junction (NVJ) and that this is crucial for maintaining proper nuclear shape and ER membrane organization. Here we show that disruption of the NVJ does not block the translocation and internalization of lipid droplets into the vacuole for their degradation, which takes place at later stages of starvation. We propose that alternative pathways of lipid droplet translocation from the ER to the vacuole may exist to enable stationary phase-induced lipophagy.
Language	English
Publishing date	2016-06-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2451097-X
ISSN	1942-0889
ISSN	1942-0889
DOI	10.1080/19420889.2016.1183854
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Article ; Online: Spatial distribution of lipid droplets during starvation

Antonio Daniel Barbosa / Symeon Siniossoglou

Communicative & Integrative Biology, Vol 9, Iss

Implications for lipophagy

2016 Volume 4

Abstract	Survival during starvation depends largely on metabolic energy, which is stored in the form of neutral lipids in specialized organelles known as lipid droplets. The precursors for the synthesis of neutral lipids are also used for membrane biogenesis, which is required for cell growth and proliferation. Therefore cells must possess mechanisms to preferentially channel lipid precursors toward either membrane synthesis or lipid droplet storage, in response to nutrient status. How this partitioning is spatially regulated within the endoplasmic reticulum (ER) where lipid droplets co-localize, remains poorly understood. We have recently shown that at the onset of starvation lipid droplets concentrate at a perinuclear ER subdomain flanking the nucleus-vacuole junction (NVJ) and that this is crucial for maintaining proper nuclear shape and ER membrane organization. Here we show that disruption of the NVJ does not block the translocation and internalization of lipid droplets into the vacuole for their degradation, which takes place at later stages of starvation. We propose that alternative pathways of lipid droplet translocation from the ER to the vacuole may exist to enable stationary phase-induced lipophagy.
Keywords	lipid droplets ; lipophagy ; nuclear membrane ; nucleus-vacuole junction ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2016-07-01T00:00:00Z
Publisher	Taylor & Francis Group
Document type	Article ; Online
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Article ; Online: An Erg11 lanosterol 14-α-demethylase-Arv1 complex is required for Candida albicans virulence.

Villasmil, Michelle L / Barbosa, Antonio Daniel / Cunningham, Jessie Lee / Siniossoglou, Symeon / Nickels, Joseph T

PloS one

2020 Volume 15, Issue 7, Page(s) e0235746

Abstract: Azole resistant fungal infections remain a health problem for the immune compromised. Current therapies are limited due to rises in new resistance mechanisms. Therefore, it is important to identify new drug targets for drug discovery and novel ... ...

Abstract	Azole resistant fungal infections remain a health problem for the immune compromised. Current therapies are limited due to rises in new resistance mechanisms. Therefore, it is important to identify new drug targets for drug discovery and novel therapeutics. Arv1 (are1 are2 required for viability 1) function is highly conserved between multiple pathogenic fungal species. Candida albicans (C. albicans) cells lacking CaArv1 are azole hypersusceptible and lack virulence. Saccharomyces cerevisiae (S. cerevisiae) Scarv1 cells are also azole hypersusceptible, a phenotype reversed by expression of CaArv1, indicating conservation in the molecular mechanism for azole susceptibility. To define the relationship between Arv1 function and azole susceptibility, we undertook a structure/function analysis of ScArv1. We identified several conserved amino acids within the ScArv1 homology domain (ScAhd) required for maintaining normal azole susceptibility. Erg11 lanosterol 14-α-demethylase is the rate-limiting enzyme in sterol biosynthesis and is the direct target of azole antifungals, so we used our ScArv1 mutants in order to explore the relationship between ScArv1 and ScErg11. Specific ScArv1 mutants ectopically expressed from a low copy plasmid were unable to restore normal azole susceptibility to Scarv1 cells and had reduced Erg11 protein levels. Erg11 protein stability depended on its ability to form a heterodimeric complex with Arv1. Complex formation was required for maintaining normal azole susceptibility. Scarv1 cells expressing orthologous CaArv1 mutants also had reduced CaErg11 levels, were unable to form a CaArv1-CaErg11 complex, and were azole hypersusceptible. Scarv1 cells expressing CaArv1 mutants unable to interact with CaErg11 could not sustain proper levels of the azole resistant CaErg11Y132F F145L protein. Caarv1/Caarv1 cells expressing CaArv1 mutants unable to interact with CaErg11 were found to lack virulence using a disseminated candidiasis mouse model. Expressing CaErg11Y132F F145L did not reverse the lack of virulence. We hypothesize that the role of Arv1 in Erg11-dependent azole resistance is to stabilize Erg11 protein level. Arv1 inhibition may represent an avenue for treating azole resistance.
MeSH term(s)	Amino Acid Sequence ; Animals ; Antifungal Agents/pharmacology ; Candida albicans/drug effects ; Candida albicans/pathogenicity ; Candidiasis/drug therapy ; Candidiasis/microbiology ; Cytochrome P-450 Enzyme System/genetics ; Cytochrome P-450 Enzyme System/metabolism ; Drug Resistance, Fungal ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Male ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice ; Mice, Inbred BALB C ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Sequence Homology ; Sterol 14-Demethylase/genetics ; Sterol 14-Demethylase/metabolism ; Virulence
Chemical Substances	ARV1 protein, S cerevisiae ; Antifungal Agents ; Fungal Proteins ; Membrane Proteins ; Saccharomyces cerevisiae Proteins ; Cytochrome P-450 Enzyme System (9035-51-2) ; Erg11 protein, S cerevisiae (EC 1.14.14.1) ; Sterol 14-Demethylase (EC 1.14.14.154)
Language	English
Publishing date	2020-07-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0235746
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