PXD026934-3

PXD026934 is an original dataset announced via ProteomeXchange.

Title	Mitochondria regulate dietary lipid processing in enterocytes
Description	Digested dietary fats are taken up, processed and transported by enterocytes to supply the body with lipids. Most absorbed lipids are assembled into pre-chylomicrons in the endoplasmic reticulum (ER) of enterocytes, which are then transported to the Golgi for maturation and subsequent secretion to the circulation. The role of mitochondria in regulating intestinal lipid transport remains unknown. Here we show that mitochondrial dysfunction in enterocytes inhibits chylomicron production and the transport of dietary lipids to peripheral organs. Mice with intestinal epithelial cell (IEC)-specific ablation of the mitochondrial-specific aspartyl - tRNA synthetase DARS2, as well as of the respiratory chain subunit SDHA or the assembly factor COX10 failed to thrive and showed massive accumulation of lipids within large lipid droplets (LDs) in enterocytes of the proximal small intestine (SI). Feeding a fat-free diet inhibited the formation of LDs in DARS2-deficient enterocytes, showing that accumulating lipids derive mostly from digested fat. Furthermore, metabolic tracing studies revealed impaired transport of dietary lipids to peripheral organs in mice lacking DARS2 in IECs. Moreover, DARS2-deficient enterocytes showed a distinct lack of mature chylomicrons concomitant with a disorganisation of the Golgi apparatus, suggesting that impaired ER to Golgi trafficking underlies impaired chylomicron production and secretion. Taken together, these results revealed a vital role of mitochondria in regulating dietary lipid transport in enterocytes, which is relevant for understanding the intestinal and nutritional defects observed in patients with mitochondrial defects.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:18:16.296.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Theresa Bock
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-25 03:55:18	ID requested
1	2023-12-21 00:39:06	announced
2	2024-01-29 06:55:00	announced	2024-01-29: Updated project metadata.
⏵ 3	2024-10-22 06:18:17	announced	2024-10-22: Updated project metadata.

10.1038/s41586-023-06857-0;

Moschandrea C, Kondylis V, Evangelakos I, Herholz M, Schneider F, Schmidt C, Yang M, Ehret S, Heine M, Jaeckstein MY, Szczepanowska K, Schwarzer R, Baumann L, Bock T, Nikitopoulou E, Brodesser S, Kr, ü, ger M, Frezza C, Heeren J, Trifunovic A, Pasparakis M, Mitochondrial dysfunction abrogates dietary lipid processing in enterocytes. Nature, 625(7994):385-392(2024) [pubmed]

10.1038/S41586-023-06857-0;

submitter keyword: Golgi, lipid metabolism,mitochondria, small intestine, enterocyctes, DARS2, ER

Manolis Pasparakis
contact affiliation	1Institute for Genetics, University of Cologne, Cologne, Germany. 2Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. 3Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany.
contact email	pasparakis@uni-koeln.de
lab head
Theresa Bock
contact affiliation	CECAD Research Center, University of Cologne
contact email	tbock2@uni-koeln.de
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/2023/12/PXD026934

PRIDE project URI

• PRIDE
  1. PXD026934
     1. Label: PRIDE project
     2. Name: Mitochondria regulate dietary lipid processing in enterocytes