PXD007158

PXD007158 is an original dataset announced via ProteomeXchange.

Title	HELA cells Sphingolipid pulldown (Cers6 and Cers5)
Description	Ectopic lipid deposition and altered mitochondrial dynamics contribute to the development of obesity and insulin resistance. However, the mechanistic link between both processes remains unclear. Here we demonstrate that abrogation of ceramide synthase (CerS)6, which generates C16:0-sphingolipids, but not of the alternative C16:0-sphingolipid synthetizing CerS5 protects from obesity and insulin resistance, and both enzymes regulate C16:0-sphingolipid synthesis in distinct intracellular compartments. Moreover, we identify proteins, which specifically interact with C16:0-sphingolipids derived from CerS5 or CerS6. Here, only CerS6-derived C16:0-sphingolipids bind the mitochondrial fission factor (Mff). CerS6- and Mff-deficiency protects from fatty acid-induced mitochondrial fragmentation in vitro, and both proteins genetically interact in vivo in obesity-induced mitochondrial fragmentation and development of insulin resistance. Our experiments reveal an unprecedented specificity of sphingolipid-signaling depending on specific synthetizing enzymes, provide a mechanistic link between lipid deposition and mitochondrial dynamics in obesity, and define the CerS6/sphingolid/Mff interaction as a therapeutic target for obesity and diabetes.
HostingRepository	PRIDE
AnnounceDate	2019-05-20
AnnouncementXML	Submission_2019-06-05_00:21:06.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hendrik Nolte
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-07-31 06:53:23	ID requested
1	2019-05-20 09:28:12	announced
⏵ 2	2019-06-05 00:21:07	announced	Updated publication reference for PubMed record(s): 31150623.

Hammerschmidt P, Ostkotte D, Nolte H, Gerl MJ, Jais A, Brunner HL, Sprenger HG, Awazawa M, Nicholls HT, Turpin-Nolan SM, Langer T, Kr, ü, ger M, Br, ü, gger B, Br, ü, ning JC, CerS6-Derived Sphingolipids Interact with Mff and Promote Mitochondrial Fragmentation in Obesity. Cell, 177(6):1536-1552.e23(2019) [pubmed]

curator keyword: Biological

submitter keyword: HELA, Cers5, Cer6, Sphingolipid, Click chemistry

Marcus Krueger
contact affiliation	Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany
contact email	marcus.krueger@uni-koeln.de
lab head
Hendrik Nolte
contact affiliation	Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD)
contact email	h.nolte@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/2019/05/PXD007158

PRIDE project URI

• PRIDE
  1. PXD007158
     1. Label: PRIDE project
     2. Name: HELA cells Sphingolipid pulldown (Cers6 and Cers5)