Proximity proteomics reveals a mechanism of fatty acid transfer at lipid droplet-mitochondria- endoplasmic reticulum contact sites

A Bezawork-Geleta; CJ Devereux; SN Keenan; J Lou; E Cho; S Nie; DP De Souza; VK Narayana; NA Siddall; CHM Rodrigues; S Portelli; T Zheng; HT Nim; M Ramialison; GR Hime; GT Dodd; E Hinde; DB Ascher; DA Stroud; MJ Watt

Journal article

Proximity proteomics reveals a mechanism of fatty acid transfer at lipid droplet-mitochondria- endoplasmic reticulum contact sites

A Bezawork-Geleta, CJ Devereux, SN Keenan, J Lou, E Cho, S Nie, DP De Souza, VK Narayana, NA Siddall, CHM Rodrigues, S Portelli, T Zheng, HT Nim, M Ramialison, GR Hime, GT Dodd, E Hinde, DB Ascher, DA Stroud, MJ Watt

Nature Communications | Published : 2025

DOI: 10.1038/s41467-025-57405-5

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Abstract

Membrane contact sites between organelles are critical for the transfer of biomolecules. Lipid droplets store fatty acids and form contacts with mitochondria, which regulate fatty acid oxidation and adenosine triphosphate production. Protein compartmentalization at lipid droplet-mitochondria contact sites and their effects on biological processes are poorly described. Using proximity-dependent biotinylation methods, we identify 71 proteins at lipid droplet-mitochondria contact sites, including a multimeric complex containing extended synaptotagmin (ESYT) 1, ESYT2, and VAMP Associated Protein B and C (VAPB). High resolution imaging confirms localization of this complex at the interface of lip..

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