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PXD028541

PXD028541 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePerilipin 5-mediated lipid droplet-mitochondria coupling determines mitochondrial capacity
DescriptionDisturbances 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.
HostingRepositoryPRIDE
AnnounceDate2022-02-11
AnnouncementXMLSubmission_2022-02-11_06:41:10.562.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterNatalia Kunowska
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-09-16 06:43:21ID requested
12022-02-11 06:33:53announced
22022-02-11 06:41:11announced2022-02-11: Updated publication reference for PubMed record(s): 35065923.
Publication List
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]
Keyword List
submitter keyword: PLIN5, mitochondria, lipid droplet, fatty acid metabolism
Contact List
Urlich Stelzl
contact affiliationInstitut für Pharmazeutische Wissenschaften, Universitry of Graz, Austria
contact emailulrich.stelzl@uni-graz.at
lab head
Natalia Kunowska
contact affiliationInstitute of Pharmaceutical Sciences University of Graz
contact emailnatalia.kunowska@uni-graz.at
dataset submitter
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