All intact cells, and their organelles, are surrounded by a ∼30 Å hydrophobic film that typically separates the interior from the environment. This film is composed of lipid bilayers that form from a pool of structurally highly diverse, amphipathic lipids. The specific composition and nature of these lipids strongly contributes to many different processes in the cell by influencing membrane structures, membrane protein sorting and functionalities. In this review, we discuss strategies to alter membrane lipid compositions of organelles and plasma membranes in different organisms, focusing on microbial cells. Reflecting the many essential roles of lipids in cellular regulation, we delineate diverse cellular processes affected by membrane lipid modifications and discuss possible applications in a biotechnological and biomedical context. A major motivation for membrane lipid engineering has been the improvement of expression, translocation and activity of heterologous membrane proteins, which can facilitate the biochemical and structural characterization of this challenging class of proteins. Additionally, better expression of membrane proteins or membrane lipid engineering - or a combination of both - led to improved production of high-value compounds and food additives, e.g. polyunsaturated fatty acids and glycolipids, in diverse hosts. More recently it has been shown that diverse cellular pathologies such as cancer and Alzheimer's disease are associated with lipid alterations. Hence, the progress in our understanding of membrane structure, function and protein-lipid interactions, and the resulting possibilities regarding the engineering of membrane lipid composition clearly enable novel nutraceutical and pharmaceutical interventions to be developed. Significant progress in this important area of research is highlighted in this review.
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http://dx.doi.org/10.1016/j.ymeth.2018.06.009 | DOI Listing |
J Biomol Struct Dyn
January 2025
College of Applied Medical Sciences, lmam Abdulrahman Bin Faisal University (lAU), Dammam, Saudi Arabia.
The present study explores the conformational dynamics of the membrane protein of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) within the Endoplasmic Reticulum-Golgi Intermediate Compartment (ERGIC) complex using an all-atomistic molecular dynamics simulation approach. Significant structural changes were observed in the N-terminal, C-terminal, transmembrane, and beta-sheet sandwich domains of the MERS-CoV membrane protein. This study also highlights the structural similarities between the MERS-CoV and the SARS-CoV-2 membrane proteins, particularly in how both exhibit a distinct kink in the transmembrane helix caused by aromatic residue-lipid interactions.
View Article and Find Full Text PDFAnticancer Agents Med Chem
January 2025
Cancer Center, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China.
Dysregulated lipid metabolism within the tumor microenvironment (TME) is a critical hallmark of cancer progression, with lipids serving as a major energy source for tumor cells. Beyond their role in cell membrane synthesis, lipids also provide essential substrates for biomolecule production and activate signaling pathways that regulate various cellular processes. Aberrant lipid metabolism impacts not only function but also alters the behavior of immune and stromal cells within the TME.
View Article and Find Full Text PDFAging (Albany NY)
January 2025
School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan.
One of the key hallmarks of Parkinson's disease is the disruption of lipid homeostasis in the brain, which plays a critical role in neuronal membrane integrity and function. Understanding how treadmill training impacts lipid restructuring and its subsequent influence on motor function could provide a basis for developing targeted non-pharmacological interventions for individuals living with early stage of PD. This study aims to investigate the effects of a treadmill training intervention on motor deficits induced by 6-OHDA in rats model of PD.
View Article and Find Full Text PDFBiochemistry
January 2025
Molecular Biophysics Laboratory, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal 462066, India.
The mitochondrial outer membrane (OMM) β-barrel proteins link the mitochondrion with the cytosol, endoplasmic reticulum, and other cellular membranes, establishing cellular homeostasis. Their active insertion and assembly in the outer mitochondrial membrane is achieved in an energy-independent yet highly effective manner by the Sorting and Assembly Machinery (SAM) of the OMM. The core SAM constituent is the 16-stranded transmembrane β-barrel Sam50.
View Article and Find Full Text PDFAnal Chem
January 2025
The Institute for Advanced Studies, Wuhan University, Wuhan, Hubei 430072, China.
The position and configuration of the C═C bond have a significant impact on the spatial conformation of unsaturated lipids, which subsequently affects their biological functions. Double bond isomerization of lipids is an important mechanism of bacterial stress response, but its in-depth mechanistic study still lacks effective analytical tools. Here, we developed a visible-light-activated dual-pathway reaction system that enables simultaneous [2 + 2] cycloaddition and catalytic - isomerization of the C═C bond of unsaturated lipids via directly excited anthraquinone radicals.
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