Summary of Study ST002710

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 PR001680. The data can be accessed directly via it's Project DOI: 10.21228/M8JH82 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

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 IDST002710
Study TitleUncoupled glycerol-3-phosphate shuttle in kidney cancer reveals that cytosolic GPD is essential to support lipid synthesis
Study SummaryThe glycerol-3-phosphate shuttle (G3PS) is a major NADH shuttle that regenerates reducing equivalents in the cytosol and produces energy in the mitochondria. Here, we demonstrate that G3PS is uncoupled in kidney cancer cells where the cytosolic reaction is 4.5 times faster than the mitochondrial reaction. The high flux through cytosolic glycerol-3-phosphate dehydrogenase (GPD) is required to maintain redox balance and support lipid synthesis. Interestingly, inhibition of G3PS by knocking down mitochondrial GPD (GPD2) has no effect on mitochondrial respiration. Instead, loss of GPD2 upregulates cytosolic GPD on a transcriptional level and promotes cancer cell proliferation by increasing glycerol-3-phosphate supply. The proliferative advantage of GPD2 knockdown tumor can be abolished by pharmacologic inhibition of lipid synthesis. Taken together, our results suggest that G3PS is not required to run as an intact NADH shuttle but is instead truncated to support complex lipid synthesis in kidney cancer.
Institute
Harvard Medical School
Last NameYao
First NameConghui
AddressLHRRB RM301, 240 Longwood Ave, Boston, MA, 02115, USA
Emailconghui_yao@hms.harvard.edu
Phone6174326865
Submit Date2023-05-11
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2023-06-06
Release Version1
Conghui Yao Conghui Yao
https://dx.doi.org/10.21228/M8JH82
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001680
Project DOI:doi: 10.21228/M8JH82
Project Title:Uncoupled glycerol-3-phosphate shuttle in kidney cancer reveals that cytosolic GPD is essential to support lipid synthesis
Project Summary:The glycerol-3-phosphate shuttle (G3PS) is a major NADH shuttle that regenerates reducing equivalents in the cytosol and produces energy in the mitochondria. Here, we demonstrate that G3PS is uncoupled in kidney cancer cells where the cytosolic reaction is 4.5 times faster than the mitochondrial reaction. The high flux through cytosolic glycerol-3-phosphate dehydrogenase (GPD) is required to maintain redox balance and support lipid synthesis. Interestingly, inhibition of G3PS by knocking down mitochondrial GPD (GPD2) has no effect on mitochondrial respiration. Instead, loss of GPD2 upregulates cytosolic GPD on a transcriptional level and promotes cancer cell proliferation by increasing glycerol-3-phosphate supply. The proliferative advantage of GPD2 knockdown tumor can be abolished by pharmacologic inhibition of lipid synthesis. Taken together, our results suggest that G3PS is not required to run as an intact NADH shuttle but is instead truncated to support complex lipid synthesis in kidney cancer.
Institute:Harvard Medical School
Last Name:Yao
First Name:Conghui
Address:LHRRB RM301, 240 Longwood Ave, Boston, MA, 02115, USA
Email:conghui_yao@hms.harvard.edu
Phone:6174326865

Subject:

Subject ID:SU002815
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Genotype Strain:balb/c
Age Or Age Range:6 week old
Gender:Female

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Treatment
SA272394091622_RPLC_POS_45C_0029FSG67
SA272395091622_RPLC_POS_37C_0008FSG67
SA272396091622_RPLC_POS_40C_0013FSG67
SA272397091622_RPLC_POS_42C_0021FSG67
SA272398091622_RPLC_POS_43C_0024FSG67
SA272399091622_RPLC_POS_36C_0005FSG67
SA272400091622_RPLC_POS_41C_0016FSG67
SA272401091622_RPLC_POS_36KD_0006FSG67
SA272402091622_RPLC_POS_43KD_0023FSG67
SA272403091622_RPLC_POS_45KD_0030FSG67
SA272404091622_RPLC_POS_42KD_0022FSG67
SA272405091622_RPLC_POS_41KD_0015FSG67
SA272406091622_RPLC_POS_44C_0037FSG67
SA272407091622_RPLC_POS_40KD_0014FSG67
SA272408091622_RPLC_POS_37KD_0007FSG67
SA272409091622_RPLC_POS_3NTC_0032NA
SA272410091622_RPLC_POS_3NTKD_0031NA
SA272411091622_RPLC_POS_32KD_0025PBS
SA272412091622_RPLC_POS_33KD_0028PBS
SA272413091622_RPLC_POS_35KD_0036PBS
SA272414091622_RPLC_POS_31KD_0020PBS
SA272415091622_RPLC_POS_34KD_0033PBS
SA272416091622_RPLC_POS_26KD_0004PBS
SA272417091622_RPLC_POS_31C_0019PBS
SA272418091622_RPLC_POS_32C_0026PBS
SA272419091622_RPLC_POS_30C_0018PBS
SA272420091622_RPLC_POS_29C_0011PBS
SA272421091622_RPLC_POS_27C_0010PBS
SA272422091622_RPLC_POS_33C_0027PBS
SA272423091622_RPLC_POS_34C_0034PBS
SA272424091622_RPLC_POS_28KD_0038PBS
SA272425091622_RPLC_POS_29KD_0012PBS
SA272426091622_RPLC_POS_27KD_0009PBS
SA272427091622_RPLC_POS_26C_0003PBS
SA272428091622_RPLC_POS_35C_0035PBS
SA272429091622_RPLC_POS_30KD_0017PBS
Showing results 1 to 36 of 36

Collection:

Collection ID:CO002808
Collection Summary:Tumors were homogenized and extracted with water methanol and chloroform. The chloroform phase was dried and reconstituted in methanol: chloroform (9:1)
Sample Type:Renal cancer cells

Treatment:

Treatment ID:TR002824
Treatment Summary:Mice were treated with PBS control or 0.1mg FSG67 i.p. daily as the paper described (DOI:10.1016/j.molcel.2023.03.023).

Sample Preparation:

Sampleprep ID:SP002821
Sampleprep Summary:Tumor samples were quenched and extracted with a mixture of water, methanol and chloroform. The water-methanol phase containing polar metabolites was dried down and reconstituted with water/acetonitrile (1:1) with the volume normalized to tumor wet weight. The chloroform phase containing lipids was dried down and reconstituted with methanol/ chloroform (9:1).

Combined analysis:

Analysis ID AN004392
Analysis type MS
Chromatography type Reversed phase
Chromatography system Agilent QTOF 6546
Column Phenomenex Kinetex C18 (150 x 2.1mm,2.6um)
MS Type ESI
MS instrument type QTOF
MS instrument name Agilent 6545 QTOF
Ion Mode POSITIVE
Units Peak area

Chromatography:

Chromatography ID:CH003295
Instrument Name:Agilent QTOF 6546
Column Name:Phenomenex Kinetex C18 (150 x 2.1mm,2.6um)
Column Temperature:40
Flow Gradient:5% B-100% 5-25min, 100% B 25-30min
Flow Rate:0.2mL/min
Solvent A:95% water/5% methanol; 5mM ammonium acetate, pH 6.5
Solvent B:95% isopropanol/5% methanol
Chromatography Type:Reversed phase

MS:

MS ID:MS004141
Analysis ID:AN004392
Instrument Name:Agilent 6545 QTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:data processed with XCMS with below settings pw = c(10,60); ppm = 5; bw = 5; method = 'centWave' method = 'obiwarp'
Ion Mode:POSITIVE
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