Ontology highlight
ABSTRACT: Lipid transfer proteins (LTPs) maintain the specialised lipid compositions of biological membranes, and many are associated with disease. In eukaryotes, they support organellar functions by transporting lipids between compartmentalised metabolic pathways. However, for the majority of the hundreds of human LTPs, the cargoes remain unknown. We combined biochemical, lipidomic and computational methods to characterize LTP-lipid complexes assembled in cellulo and in an in vitro biochemical assay. We identified bound lipids for about half of the LTPs analysed, and confirmed known cargoes, while discovering new ones for most LTP families. The data represents a systematic resource that captures the general principles of non-vesicular lipid transport in humans. The specificity of LTPs for lipids involves not only the recognition of specific head groups, but also of specific acyl chains. This selectivity defines lipid species within a lipid class with different metabolic or functional fates. The generalised ability of LTPs to form complexes with more than one class of lipids delineates new relationships between lipids and regulatory mechanisms that may contribute to the coordination of metabolism between different organelles. This work represents a resource and a framework for further analyses in different cell types, in pathological states or following various cellular perturbations.
INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase
PROVIDER: MTBLS9567 | MetaboLights | 2025-11-14
REPOSITORIES: MetaboLights
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Nature 20260107
Lipid transfer proteins (LTPs) maintain the specialized lipid compositions of organellar membranes<sup>1,2</sup>. In humans, many LTPs are implicated in diseases<sup>3</sup>, but the cargo and auxiliary lipids that facilitate the transfer of the majority of LTPs remain unknown. Here we combined biochemical, lipidomic and computational methods to systematically characterize LTP-lipid complexes<sup>4</sup> and measure how LTP gains of function affect cellular lipidomes. We identified bound lipids ...[more]