Lipid Adaptability and Organelle Integrity: Mechanisms of Membrane Remodelling and Homeostasis

Membrane lipids are crucial determinants of organelle identity and compartmentalized functions. A defining feature of organelle lipid metabolism is its profound adaptability. When lipid homeostasis is disrupted, cells deploy robust, redundant compensatory mechanisms to maintain membrane integrity. The immense structural diversity of lipid species allows cells to remodel their membranes, utilizing alternative lipids to substitute with biophysically comparable missing components. Furthermore, membrane contact sites (MCSs) establish close membrane appositions between distinct organelles. This highly interconnected network allows for the rapid, non-vesicular exchange of lipids alongside traditional vesicular trafficking, enabling organelles to quickly compensate for local lipid deficits or membrane damage by drawing resources from neighbouring compartments.Due to these highly adaptive systems, defining the precise functions of individual lipid-modifying enzymes or lipid transfer proteins has been notoriously challenging. Genetic knockouts trigger widespread cellular perturbations, allowing time for the activation of compensatory networks that include massive lipid sharing via MCSs and extensive transcriptional rewiring. Consequently, these genetic models frequently result in either complete lethality or no discernible phenotype, thereby difficult to understand the primary physiological function of the targeted protein. In contrast, acute chemical inhibitors can instantly perturb specific lipid-modifying enzymes or proteins before the cell can deploy these compensatory networks, offering a powerful strategy to capture immediate, primary cellular phenotypes.To accurately understand organelle membrane biology, we must bypass the cell’s long-term adaptation pathways. By employing short-term, acute perturbations to target specific lipid systems, such as degron-mediated rapid and selective degradation of enzymes or transporters we can observe the direct, immediate effects of altered lipid environments on organelle function before complex compensatory networks obscure the primary biological mechanisms. This Research Topic aims to feature multidisciplinary research that explores how cells preserve membrane lipid balance under stress and how acutely disturbing these processes can illuminate core mechanisms of lipid regulation and organelle integrity. We welcome original research, brief research reports, reviews, methods articles, and perspectives that investigate the molecular logic and physiological implications of lipid adaptability in cell biology.Areas to be covered might include, but are not limited to:• Organelle membrane remodelling and adaptation: Molecular mechanisms of lipid remodelling and compartmental adaptation; and structural and functional consequences of altered lipid composition on organelle identity• Inter-organelle communication: Vesicular versus non-vesicular lipid transfer pathways under physiological or stressed states• Perturbation dynamics: Distinct outcomes of acute versus chronic perturbation of lipid metabolism; and the development of novel chemical biology tools or optogenetic strategies to elucidate lipid function• Membrane biophysics and structure: Lipid–protein interactions in shaping membrane curvature and dynamics; and advanced biophysical modelling and imaging approaches for studying membrane lipid homeostasis• Systems biology and signalling: High-throughput omics-based profiling (lipidomics, proteomics) of membrane and organelle states; and transcriptional and signalling responses to lipid imbalance Topic editors: Yeun Ju Kim, Ludovic Enkler Source: https://www.frontiersin.org/research-topics/82899/lipid-adaptability-and-organelle-integrity-mechanisms-of-membrane-remodelling-and-homeostasis