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.
| Study ID | ST002710 |
| Study Title | Uncoupled glycerol-3-phosphate shuttle in kidney cancer reveals that cytosolic GPD is essential to support lipid synthesis |
| Study 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 |
| conghui_yao@hms.harvard.edu | |
| Phone | 6174326865 |
| Submit Date | 2023-05-11 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-06-06 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
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 |
| Species Group: | Mammals |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Treatment |
|---|---|---|
| SA272394 | 091622_RPLC_POS_45C_0029 | FSG67 |
| SA272395 | 091622_RPLC_POS_37C_0008 | FSG67 |
| SA272396 | 091622_RPLC_POS_40C_0013 | FSG67 |
| SA272397 | 091622_RPLC_POS_42C_0021 | FSG67 |
| SA272398 | 091622_RPLC_POS_43C_0024 | FSG67 |
| SA272399 | 091622_RPLC_POS_36C_0005 | FSG67 |
| SA272400 | 091622_RPLC_POS_41C_0016 | FSG67 |
| SA272401 | 091622_RPLC_POS_36KD_0006 | FSG67 |
| SA272402 | 091622_RPLC_POS_43KD_0023 | FSG67 |
| SA272403 | 091622_RPLC_POS_45KD_0030 | FSG67 |
| SA272404 | 091622_RPLC_POS_42KD_0022 | FSG67 |
| SA272405 | 091622_RPLC_POS_41KD_0015 | FSG67 |
| SA272406 | 091622_RPLC_POS_44C_0037 | FSG67 |
| SA272407 | 091622_RPLC_POS_40KD_0014 | FSG67 |
| SA272408 | 091622_RPLC_POS_37KD_0007 | FSG67 |
| SA272409 | 091622_RPLC_POS_3NTC_0032 | NA |
| SA272410 | 091622_RPLC_POS_3NTKD_0031 | NA |
| SA272411 | 091622_RPLC_POS_32KD_0025 | PBS |
| SA272412 | 091622_RPLC_POS_33KD_0028 | PBS |
| SA272413 | 091622_RPLC_POS_35KD_0036 | PBS |
| SA272414 | 091622_RPLC_POS_31KD_0020 | PBS |
| SA272415 | 091622_RPLC_POS_34KD_0033 | PBS |
| SA272416 | 091622_RPLC_POS_26KD_0004 | PBS |
| SA272417 | 091622_RPLC_POS_31C_0019 | PBS |
| SA272418 | 091622_RPLC_POS_32C_0026 | PBS |
| SA272419 | 091622_RPLC_POS_30C_0018 | PBS |
| SA272420 | 091622_RPLC_POS_29C_0011 | PBS |
| SA272421 | 091622_RPLC_POS_27C_0010 | PBS |
| SA272422 | 091622_RPLC_POS_33C_0027 | PBS |
| SA272423 | 091622_RPLC_POS_34C_0034 | PBS |
| SA272424 | 091622_RPLC_POS_28KD_0038 | PBS |
| SA272425 | 091622_RPLC_POS_29KD_0012 | PBS |
| SA272426 | 091622_RPLC_POS_27KD_0009 | PBS |
| SA272427 | 091622_RPLC_POS_26C_0003 | PBS |
| SA272428 | 091622_RPLC_POS_35C_0035 | PBS |
| SA272429 | 091622_RPLC_POS_30KD_0017 | PBS |
| 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 |
