PXD060912

PXD060912 is an original dataset announced via ProteomeXchange.

Title	Proximity proteomics reveals a mechanism of fatty acid transfer at lipid droplet-mitochondria- endoplasmic reticulum contact sites
Description	Membrane contact sites between organelles are critical for 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 lipid droplet-mitochondria-endoplasmic reticulum where it likely transfers fatty acids to enable -oxidation. Deletion of ESYT1, ESYT2 or VAPB limits lipid droplet-derived fatty acid oxidation, resulting in depletion of tricarboxylic acid cycle metabolites, remodeling of the cellular lipidome, and induction of lipotoxic stress. These findings were recapitulated in Esyt1 and Esyt2 deficient mice. Our study uncovers a fundamental mechanism that is required for lipid droplet-derived fatty acid oxidation and cellular lipid homeostasis, with implications for metabolic diseases and survival.
HostingRepository	PRIDE
AnnounceDate	2025-04-28
AnnouncementXML	Submission_2025-04-27_17:20:24.239.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Stroud
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-18 01:38:18	ID requested
⏵ 1	2025-04-27 17:20:25	announced

10.1038/s41467-025-57405-5;

Bezawork-Geleta A, Devereux CJ, Keenan SN, Lou J, Cho E, Nie S, De Souza DP, Narayana VK, Siddall NA, Rodrigues CHM, Portelli S, Zheng T, Nim HT, Ramialison M, Hime GR, Dodd GT, Hinde E, Ascher DB, Stroud DA, Watt MJ, Proximity proteomics reveals a mechanism of fatty acid transfer at lipid droplet-mitochondria- endoplasmic reticulum contact sites. Nat Commun, 16(1):2135(2025) [pubmed]

submitter keyword: lipid droplet, fatty acid, lipid metabolism, lipidomics, lipotoxicity, mitochondria, cell metabolism

David Stroud
contact affiliation	Department of Biochemistry and Pharmacology, the University of Melbourne, Parkville, Victoria 3052, Australia
contact email	david.stroud@unimelb.edu.au
lab head
David Stroud
contact affiliation	The University of Melbourne
contact email	david.stroud@unimelb.edu.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/04/PXD060912

PRIDE project URI

• PRIDE
  1. PXD060912
     1. Label: PRIDE project
     2. Name: Proximity proteomics reveals a mechanism of fatty acid transfer at lipid droplet-mitochondria- endoplasmic reticulum contact sites