The oily nucleus– role of phospholipids in genome biology: membrane-directed roles and signaling in the nucleoplasm

Abstract Phospholipids, widely known for their structural role in cellular membranes, are now also recognized to play pivotal roles in signal transduction, metabolism, and cellular homeostasis. However, the nucleus is often overlooked in the context of phospholipid biology. The dynamic abundance and...

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Main Authors: Zobia Umair, Zahid Nawaz, Sumaiya Hasnain, Wolfgang Fischle
Format: Article
Language:English
Published: Springer 2025-07-01
Series:Cellular and Molecular Life Sciences
Subjects:
Online Access:https://doi.org/10.1007/s00018-025-05825-3
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author Zobia Umair
Zahid Nawaz
Sumaiya Hasnain
Wolfgang Fischle
author_facet Zobia Umair
Zahid Nawaz
Sumaiya Hasnain
Wolfgang Fischle
author_sort Zobia Umair
collection DOAJ
description Abstract Phospholipids, widely known for their structural role in cellular membranes, are now also recognized to play pivotal roles in signal transduction, metabolism, and cellular homeostasis. However, the nucleus is often overlooked in the context of phospholipid biology. The dynamic abundance and precise management of the turnover of nuclear phospholipids by dedicated kinases, phosphatases, and phospholipases implies specialized functions. Like the cytoplasm, many of these biological roles occur or are initiated within the nuclear membrane. However, several aspects of nuclear phospholipid biology appear to be based in the nucleoplasm and are mediated by dynamic and soluble lipoprotein complexes. In many cases, the exact working spaces and molecular mechanisms of action of nuclear phospholipids are not yet clearly defined, and their physiology is likely underestimated due to technical challenges. Nonetheless, in recent years, the impact of nuclear phospholipids on the structure and function of the genome has been found to be more multifaceted and complex. In this review, we summarize recent insights into the interactions and biological roles of phospholipids with respect to chromatin, gene regulation, and nuclear physiology, and discuss these roles in the context of two broad functional domains – the nuclear membrane and the nucleoplasm. We argue that a more detailed understanding of the molecular working modes of nuclear phospholipids is crucial to enable their full scientific comprehension, especially when the exploration of the biology of nuclear phospholipids and their dysregulation may offer promising avenues for diagnosis and therapeutic interventions for various genome-linked diseases.
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publishDate 2025-07-01
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spelling doaj-art-eb9c2dba1c4e4b1d8070fa64c5c7d2b72025-08-20T04:01:52ZengSpringerCellular and Molecular Life Sciences1420-90712025-07-0182111610.1007/s00018-025-05825-3The oily nucleus– role of phospholipids in genome biology: membrane-directed roles and signaling in the nucleoplasmZobia Umair0Zahid Nawaz1Sumaiya Hasnain2Wolfgang Fischle3Bioscience Program, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST)Bioscience Program, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST)Bioscience Program, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST)Bioscience Program, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST)Abstract Phospholipids, widely known for their structural role in cellular membranes, are now also recognized to play pivotal roles in signal transduction, metabolism, and cellular homeostasis. However, the nucleus is often overlooked in the context of phospholipid biology. The dynamic abundance and precise management of the turnover of nuclear phospholipids by dedicated kinases, phosphatases, and phospholipases implies specialized functions. Like the cytoplasm, many of these biological roles occur or are initiated within the nuclear membrane. However, several aspects of nuclear phospholipid biology appear to be based in the nucleoplasm and are mediated by dynamic and soluble lipoprotein complexes. In many cases, the exact working spaces and molecular mechanisms of action of nuclear phospholipids are not yet clearly defined, and their physiology is likely underestimated due to technical challenges. Nonetheless, in recent years, the impact of nuclear phospholipids on the structure and function of the genome has been found to be more multifaceted and complex. In this review, we summarize recent insights into the interactions and biological roles of phospholipids with respect to chromatin, gene regulation, and nuclear physiology, and discuss these roles in the context of two broad functional domains – the nuclear membrane and the nucleoplasm. We argue that a more detailed understanding of the molecular working modes of nuclear phospholipids is crucial to enable their full scientific comprehension, especially when the exploration of the biology of nuclear phospholipids and their dysregulation may offer promising avenues for diagnosis and therapeutic interventions for various genome-linked diseases.https://doi.org/10.1007/s00018-025-05825-3PhospholipidsPhosphoinositidesNucleusGene expressionChromatin remodelingNuclear signaling
spellingShingle Zobia Umair
Zahid Nawaz
Sumaiya Hasnain
Wolfgang Fischle
The oily nucleus– role of phospholipids in genome biology: membrane-directed roles and signaling in the nucleoplasm
Cellular and Molecular Life Sciences
Phospholipids
Phosphoinositides
Nucleus
Gene expression
Chromatin remodeling
Nuclear signaling
title The oily nucleus– role of phospholipids in genome biology: membrane-directed roles and signaling in the nucleoplasm
title_full The oily nucleus– role of phospholipids in genome biology: membrane-directed roles and signaling in the nucleoplasm
title_fullStr The oily nucleus– role of phospholipids in genome biology: membrane-directed roles and signaling in the nucleoplasm
title_full_unstemmed The oily nucleus– role of phospholipids in genome biology: membrane-directed roles and signaling in the nucleoplasm
title_short The oily nucleus– role of phospholipids in genome biology: membrane-directed roles and signaling in the nucleoplasm
title_sort oily nucleus role of phospholipids in genome biology membrane directed roles and signaling in the nucleoplasm
topic Phospholipids
Phosphoinositides
Nucleus
Gene expression
Chromatin remodeling
Nuclear signaling
url https://doi.org/10.1007/s00018-025-05825-3
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