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Rapid ER remodeling induced by a peptide-lipid complex in dying tumor cells

Sabari, Samudra LU ; Chinchankar, Siddharth LU ; Ambite, Ines LU orcid ; Nazari, Atefeh LU ; Carneiro, António Pedro Nbm LU ; Svenningsson, Axel LU ; Svanborg, Catharina LU and Chaudhuri, Arunima LU orcid (2025) In Life Science Alliance 8(6).
Abstract

The membranous ER spans the entire cell, creating a network for the biosynthesis of proteins and lipids, cell-wide communication, and nuclear delivery of molecules, including therapeutic agents. Here, we identify a novel ER response triggered by the tumoricidal complex alpha1-oleate, defined by a loss of peripheral ER structure, extensive ER vesiculation. Alpha1-oleate was present in the ER-derived vesicle membranes, also decorated by ER-resident and ER-interacting proteins, calnexin and ORP3, and in their lumen, also enriched for KDEL, confirming their ER origin distinct from lipid droplets. Rapid nuclear uptake of the complex constituents resulted in diffuse nuclear staining, and the asymmetrical perinuclear enrichment of the... (More)

The membranous ER spans the entire cell, creating a network for the biosynthesis of proteins and lipids, cell-wide communication, and nuclear delivery of molecules, including therapeutic agents. Here, we identify a novel ER response triggered by the tumoricidal complex alpha1-oleate, defined by a loss of peripheral ER structure, extensive ER vesiculation. Alpha1-oleate was present in the ER-derived vesicle membranes, also decorated by ER-resident and ER-interacting proteins, calnexin and ORP3, and in their lumen, also enriched for KDEL, confirming their ER origin distinct from lipid droplets. Rapid nuclear uptake of the complex constituents resulted in diffuse nuclear staining, and the asymmetrical perinuclear enrichment of the collapsing ER with its content of alpha1-oleate created large invaginations lined by the ER, inner nuclear membrane markers, and lamin nucleoskeleton. In parallel, a change in nuclear shape resulted in a volcano-like structure. This newly discovered, potent ER response to alpha1-oleate may have evolved to package ER-associated cellular contents in the nuclei of dying tumor cells, thus sequestering toxic cell debris associated with apoptotic cell death.

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Please use this url to cite or link to this publication:
author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Endoplasmic Reticulum/metabolism, Cell Line, Tumor, Peptides/metabolism, Apoptosis, Oleic Acid/metabolism, Neoplasms/metabolism, Cell Nucleus/metabolism, Lipid Droplets/metabolism
in
Life Science Alliance
volume
8
issue
6
article number
e202403114
pages
21 pages
publisher
Rockefeller University Press
external identifiers
  • scopus:105001518567
  • pmid:40132886
ISSN
2575-1077
DOI
10.26508/lsa.202403114
language
English
LU publication?
yes
additional info
© 2025 Sabari et al.
id
1a3c98e2-7d3e-49d5-9b15-4c4728d3d596
date added to LUP
2025-06-10 10:14:52
date last changed
2025-06-11 04:07:00
@article{1a3c98e2-7d3e-49d5-9b15-4c4728d3d596,
  abstract     = {{<p>The membranous ER spans the entire cell, creating a network for the biosynthesis of proteins and lipids, cell-wide communication, and nuclear delivery of molecules, including therapeutic agents. Here, we identify a novel ER response triggered by the tumoricidal complex alpha1-oleate, defined by a loss of peripheral ER structure, extensive ER vesiculation. Alpha1-oleate was present in the ER-derived vesicle membranes, also decorated by ER-resident and ER-interacting proteins, calnexin and ORP3, and in their lumen, also enriched for KDEL, confirming their ER origin distinct from lipid droplets. Rapid nuclear uptake of the complex constituents resulted in diffuse nuclear staining, and the asymmetrical perinuclear enrichment of the collapsing ER with its content of alpha1-oleate created large invaginations lined by the ER, inner nuclear membrane markers, and lamin nucleoskeleton. In parallel, a change in nuclear shape resulted in a volcano-like structure. This newly discovered, potent ER response to alpha1-oleate may have evolved to package ER-associated cellular contents in the nuclei of dying tumor cells, thus sequestering toxic cell debris associated with apoptotic cell death.</p>}},
  author       = {{Sabari, Samudra and Chinchankar, Siddharth and Ambite, Ines and Nazari, Atefeh and Carneiro, António Pedro Nbm and Svenningsson, Axel and Svanborg, Catharina and Chaudhuri, Arunima}},
  issn         = {{2575-1077}},
  keywords     = {{Humans; Endoplasmic Reticulum/metabolism; Cell Line, Tumor; Peptides/metabolism; Apoptosis; Oleic Acid/metabolism; Neoplasms/metabolism; Cell Nucleus/metabolism; Lipid Droplets/metabolism}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{6}},
  publisher    = {{Rockefeller University Press}},
  series       = {{Life Science Alliance}},
  title        = {{Rapid ER remodeling induced by a peptide-lipid complex in dying tumor cells}},
  url          = {{http://dx.doi.org/10.26508/lsa.202403114}},
  doi          = {{10.26508/lsa.202403114}},
  volume       = {{8}},
  year         = {{2025}},
}