Summary of Study ST002335

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001498. The data can be accessed directly via it's Project DOI: 10.21228/M83D9C This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002335
Study TitlePathogenic Auxilin mutations affect lipids that are critical to Synaptojanin function
Study SummaryMass spectrometry was performed on heads of 15DO flies homogenized in 100 µl D-PBS (Dulbecco’s phosphate-buffered saline without Mg2+ and Ca2+) by Lipotype. Fifteen fly heads were pooled from three independent crosses for each analysis, and mass spectrometry was performed on n=7 for wild-type, n≥4 analyses for dAuxWT/WT, dAuxRG/RG, dAuxWT/F956x and dAuxRG/F956x and n=3 for dAuxWT/F956x and dAuxRG/F956x overexpressing Synj.
Institute
VIB-KU Leuven
Last NameJacquemyn
First NameJulie
AddressMedical Sciences Building 7-25, Edmonton, Alberta, T6H 0L2, Canada
Emailjacquemynjulie@ualberta.ca
Phone+1 (587) 3409325
Submit Date2022-10-27
Analysis Type DetailMS(Dir. Inf.)
Release Date2022-11-21
Release Version1
Julie Jacquemyn Julie Jacquemyn
https://dx.doi.org/10.21228/M83D9C
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Project:

Project ID:PR001498
Project DOI:doi: 10.21228/M83D9C
Project Title:Parkinsonism mutations in DNAJC6 cause lipid defects and neurodegeneration that are rescued by Synj1
Project Summary:Recent evidence links dysfunctional lipid metabolism to the pathogenesis of Parkinson’s disease, but the mechanisms are not resolved. Here, we generated a new Drosophila knock-in model of DNAJC6/Auxilin and find that the pathogenic mutation causes synaptic dysfunction, neurological defects and neurodegeneration, as well as specific lipid metabolism alterations. In these mutants, membrane lipids containing long-chain polyunsaturated fatty acids, including phosphatidylinositol lipid species that are key for synaptic vesicle recycling and organelle function, are reduced. Overexpression of another protein mutated in Parkinson’s disease, Synaptojanin-1, known to bind and metabolize specific phosphoinositides, rescues the DNAJC6/Auxilin lipid alterations, the neuronal function defects and neurodegeneration. Our work reveals a functional relation between two proteins mutated in Parkinsonism and implicates deregulated phosphoinositide metabolism in the maintenance of neuronal integrity and neuronal survival.
Institute:VIB-KU Leuven
Department:Department of Neurosciences
Laboratory:Laboratory of Neuronal Communication - Dr. Patrik Verstreken
Last Name:Jacquemyn
First Name:Julie
Address:Medical Sciences Building 7-25, Edmonton, Alberta, T6H 0L2, Canada
Email:jacquemynjulie@ualberta.ca
Phone:5873409325

Subject:

Subject ID:SU002423
Subject Type:Invertebrate
Subject Species:Drosophila melanogaster
Taxonomy ID:7227
Age Or Age Range:15 day old flies
Gender:Male and female

Factors:

Subject type: Invertebrate; Subject species: Drosophila melanogaster (Factor headings shown in green)

mb_sample_id local_sample_id Genotype
SA232139S2AuWT/WT
SA232140S1AuWT/WT
SA232141S4AuWT/WT
SA232142S3AuWT/WT
SA232143S16AuxRG/F956x
SA232144S15AuxRG/F956x
SA232145S19AuxRG/F956x
SA232146S18AuxRG/F956x
SA232147S17AuxRG/F956x
SA232148S7AuxRG/RG
SA232149S6AuxRG/RG
SA232150S5AuxRG/RG
SA232151S9AuxRG/RG
SA232152S8AuxRG/RG
SA232153S12AuxWT/F956x
SA232154S11AuxWT/F956x
SA232155S10AuxWT/F956x
SA232156S13AuxWT/F956x
SA232157S14AuxWT/F956x
SA232158S23UAS-synj-AuxRG/F956x
SA232159S25UAS-synj-AuxRG/F956x
SA232160S24UAS-synj-AuxRG/F956x
SA232161S22UAS-synj-AuxWT/F956x
SA232162S21UAS-synj-AuxWT/F956x
SA232163S20UAS-synj-AuxWT/F956x
SA232164S31w1118
SA232165S32w1118
SA232166S30w1118
SA232167S29w1118
SA232168S26w1118
SA232169S27w1118
SA232170S28w1118
Showing results 1 to 32 of 32

Collection:

Collection ID:CO002416
Collection Summary:Heads of 15DO flies were homogenized in 100 µl D-PBS (Dulbecco’s phosphate-buffered saline without Mg2+ and Ca2+) and stored at -80°C until processed for MS analysis by Lipotype. Fifteen fly heads were pooled from three independent crosses for each analysis, and mass spectrometry was performed on n=7 for wild-type, n≥4 analyses for dAuxWT/WT, dAuxRG/RG, dAuxWT/F956x and dAuxRG/F956x and n=3 for dAuxWT/F956x and dAuxRG/F956x overexpressing Synj.
Sample Type:Insect tissue
Storage Conditions:-80℃

Treatment:

Treatment ID:TR002435
Treatment Summary:In this study we did not apply any additional treatment(s) to the samples.

Sample Preparation:

Sampleprep ID:SP002429
Sampleprep Summary:Lipids were extracted using chloroform and methanol (1). Prior to lipid extraction, samples were spiked with lipid class-specific internal standards. After drying and resuspending in an appropriate MS acquisition mixture, lipid extracts were infused directly in QExactive mass spectrometer (Thermo Fisher Scientific) with TriVersa NanoMate ion source (Advion Biosciences). Samples are analyzed in both positive and negative ion modes, with MS resolution Rm/z=200=280000 and MSMS resolution Rm/z=200=17500, in a single acquisition. Sample preparations and analysis were done by Lipotype. (1) Sampaio, J. L. et al. Membrane lipidome of an epithelial cell line. Proceedings of the National Academy of Sciences 108, 1903–1907 (2011).

Combined analysis:

Analysis ID AN003814
Analysis type MS
Chromatography type None (Direct infusion)
Chromatography system none
Column none
MS Type ESI
MS instrument type QTRAP
MS instrument name Thermo Q Exactive Orbitrap
Ion Mode POSITIVE
Units pMol

Chromatography:

Chromatography ID:CH002821
Instrument Name:none
Column Name:none
Chromatography Type:None (Direct infusion)

MS:

MS ID:MS003556
Analysis ID:AN003814
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:QTRAP
MS Type:ESI
MS Comments:Samples are analyzed in both positive and negative ion modes, with MS resolution Rm/z=200=280000 and MSMS resolution Rm/z=200=17500, in a single acquisition. Acquired data was processed using lipid identification software based on LipidXplorer (1). Data post-processing and normalization were performed by Lipotype using a developed data management system. Data analysis was performed using GraphPad Prism software 9.3.1. Pmol values (obtained by MS) of individual lipid species were transformed into a fraction of the total PA, DAG, PI, PC, PE, and PS lipids in the sample. (1)Herzog, R. et al. Lipidxplorer: A software for consensual cross-platform lipidomics. PLoS ONE 7, e29851 (2012).
Ion Mode:POSITIVE
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