PXD028541

PXD028541 is an original dataset announced via ProteomeXchange.

Title	Perilipin 5-mediated lipid droplet-mitochondria coupling determines mitochondrial capacity
Description	Disturbances in lipid homeostasis can cause mitochondrial dysfunction and lipotoxicity requiring tight regulation of intracellular lipid metabolism and fatty acid (FA) flux. Perilipin 5 (PLIN5) decorates intracellular lipid droplets (LD) in oxidative tissues and controls triacylglycerol (TG) turnover via its interactions with Adipose triglyceride lipase (ATGL) and the ATGL co-activator Comparative gene identification-58 (CGI-58). Furthermore, PLIN5 anchors mitochondria to the LD membrane via its carboxyl-terminal domain. However, the role of this LD-mitochondria coupling (LDMC) in cellular FA flux and energy catabolism is less established. In this study, we investigated the impact of abolished LDMC on cellular FA flux, mitochondrial respiration and protein interaction. To do so, we established novel PLIN5 truncation variants lacking LDMC while maintaining normal interactions with lipolytic key players. Radiotracer studies with transgenic cell lines stably overexpressing either wild type or truncated PLIN5 revealed that LDMC has no significant impact on FA esterification upon lipid loading or TG catabolism during stimulated lipolysis. Moreover, we found that LDMC is not essential for FA shuttling into mitochondria, which was in line with only minor effects of disrupted LDMC on FA oxidation. In contrast, LDMC significantly improved the mitochondrial respiratory capacity and metabolic flexibility of lipid-challenged cardiomyocytes, which was corroborated by LDMC-dependent interactions of PLIN5 with mitochondrial proteins involved in mitochondrial respiration, dynamics and cristae organization. Taken together, this study suggests that PLIN5 preserves mitochondrial function by adjusting FA supply via the regulation of TG hydrolysis and that LDMC is a vital part of mitochondrial integrity.
HostingRepository	PRIDE
AnnounceDate	2022-02-11
AnnouncementXML	Submission_2022-02-11_06:41:10.562.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Natalia Kunowska
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-16 06:43:21	ID requested
1	2022-02-11 06:33:53	announced
⏵ 2	2022-02-11 06:41:11	announced	2022-02-11: Updated publication reference for PubMed record(s): 35065923.

Kien B, Kolleritsch S, Kunowska N, Heier C, Chalhoub G, Tilp A, Wolinski H, Stelzl U, Haemmerle G, Lipid droplet-mitochondria coupling via perilipin 5 augments respiratory capacity but is dispensable for FA oxidation. J Lipid Res, 63(3):100172(2022) [pubmed]

submitter keyword: PLIN5, mitochondria, lipid droplet, fatty acid metabolism

Urlich Stelzl
contact affiliation	Institut für Pharmazeutische Wissenschaften, Universitry of Graz, Austria
contact email	ulrich.stelzl@uni-graz.at
lab head
Natalia Kunowska
contact affiliation	Institute of Pharmaceutical Sciences University of Graz
contact email	natalia.kunowska@uni-graz.at
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/2022/02/PXD028541

PRIDE project URI

• PRIDE
  1. PXD028541
     1. Label: PRIDE project
     2. Name: Perilipin 5-mediated lipid droplet-mitochondria coupling determines mitochondrial capacity