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Cited by 65Nuclear Structure and FunctionLipid Membrane Structure and BehaviorCaveolin-1 and cellular processes

Lipid saturation controls nuclear envelope function

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Romanauska, Anete, Köhler, Alwin·2023·Nature Cell Biology
DOI 10.1038/s41556-023-01207-8PMC PMC10495262
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Abstract

The nuclear envelope (NE) is a spherical double membrane with elastic properties. How NE shape and elasticity are regulated by lipid chemistry is unknown. Here we discover lipid acyl chain unsaturation as essential for NE and nuclear pore complex (NPC) architecture and function. Increased lipid saturation rigidifies the NE and the endoplasmic reticulum into planar, polygonal membranes, which are fracture prone. These membranes exhibit a micron-scale segregation of lipids into ordered and disordered phases, excluding NPCs from the ordered phase. Balanced lipid saturation is required for NPC integrity, pore membrane curvature and nucleocytoplasmic transport. Oxygen deprivation amplifies the impact of saturated lipids, causing NE rigidification and rupture. Conversely, lipid droplets buffer saturated lipids to preserve NE architecture. Our study uncovers a fundamental link between lipid acyl chain structure and the integrity of the cell nucleus with implications for nuclear membrane malfunction in ischaemic tissues.

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  • Lipid droplets generate surface tension and rigidity sufficient to compress nuclei and disrupt cytoskeletal architecture.

    “lipid droplets (LDs), once regarded as inert metabolic depots, generate surface tension and rigidity sufficient to compress nuclei and disrupt cytoskeletal architecture [21]”

    From Liver Stiffness Rises Early in MASLD and Drives Inflammation, Lipid Dysmetabolism, and Fibrosis via Piezo1–YAP Mechanotransduction (2026) · cites this paper as [21]

    The Results section, “Lipid droplets preserve NPC and NE integrity” (page unavailable), says that increasing lipid droplets reduced abnormal nuclear-envelope shapes and helped preserve nuclear integrity—the opposite of attributing nuclear deformation to droplets. The paper attributes membrane rigidity to excess saturated lipids, not droplet surface tension, and does not report droplet-driven cytoskeletal disruption. (LLM, conf=0.89)

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Cited by

Sorted by citations

Authors
Romanauska, A., & Köhler, A.
Affiliations
University of Vienna (AT)
Corresponding author
Köhler, Alwin
ORCID
Venue
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2023-08-17
Volume
25
Issue
9
Pages
1290-1302
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
DOI
10.1038/s41556-023-01207-8
PMC
PMC10495262
OpenAlex
W4385948630
Cited by
65
References
0
Citations by year
2026: 18 · 2025: 26 · 2024: 17 · 2023: 4
FWCI
5.79
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Cell Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • NOMIS Stiftung
  • H2020 European Research Council (772032)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
Keywords
nuclear envelope, lipid saturation, acyl chain unsaturation, nuclear pore complex, membrane curvature, membrane rigidity, lipid phase separation, nuclear transport, oxygen deprivation, lipid droplets, endoplasmic reticulum, nuclear membrane rupture, ischemia
MeSH terms
Cell Nucleus, Elasticity, Lipids, Nuclear Envelope, Nuclear Pore

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