Summary of Study ST003891

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 PR002436. The data can be accessed directly via it's Project DOI: 10.21228/M8RN89 This work is supported by NIH grant, U2C- DK119886. See: https://www.metabolomicsworkbench.org/about/howtocite.php

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Study IDST003891
Study TitleRespiration defects limit serine synthesis required for lung cancer growth and survival - Effect of Polg mutation in NSCLC Tissues_Plasma
Study TypeIn vivo Isotope Tracing
Study SummaryThis study investigates the impact of mtDNA mutation burden induced by the PolGD256A mutation in NSCLC. Using in vivo, we characterized the metabolic profile of NSCLC harboring this mutation compared to controls after submitting the animals to 12 weeks of special diet and 2h30 of [U-13C]D-Glucose infusion.
Institute
Rutgers University
DepartmentRutgers Cancer Institute
LaboratoryEileen White
Last NameLopes
First NameEduardo
Address195 Little Albany Street
Emailedu.llopes@gmail.com
Phone732-235-5795
Submit Date2025-03-20
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailLC-MS
Release Date2025-05-06
Release Version1
Eduardo Lopes Eduardo Lopes
https://dx.doi.org/10.21228/M8RN89
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR002436
Project DOI:doi: 10.21228/M8RN89
Project Title:Respiration defects limit serine synthesis required for lung cancer growth and survival
Project Type:Pool Size Metabolomic in vivo
Project Summary:Mitochondrial function supports energy and anabolic metabolism. Pathogenic mitochondrial DNA (mtDNA) mutations impair these processes, causing mitochondrial diseases. Their role in human cancers is less clear; while some cancers harbor high mtDNA mutation burden, others do not. Here we show that a proofreading mutant of DNA polymerase gamma (PolGD256A) increases the mtDNA mutation burden in non-small-cell lung cancer (NSCLC). This mutation promotes the accumulation of defective mitochondria, reduces tumor cell proliferation and viability, and improves cancer survival. In NSCLC, pathogenic mtDNA mutations enhance glycolysis and create a glucose dependency to support mitochondrial energy, but at the expense of a lower NAD⁺/NADH ratio that hinders de novo serine synthesis. Thus, mitochondrial function in NSCLC is essential for maintaining adequate serine synthesis, which in turn supports the anabolic metabolism and redox homeostasis required for tumor growth, explaining why these cancers preserve functional mtDNA.
Institute:Rutgers University
Department:Rutgers Cancer Institute
Laboratory:Eileen White
Last Name:Cararo Lopes
First Name:Eduardo
Address:195 Little Albany Street
Email:edu.llopes@gmail.com
Phone:732-235-5795
Funding Source:NIH
Publications:Respiration defects limit serine synthesis required for lung cancer growth and survival

Subject:

Subject ID:SU004026
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Gender:Male and female

Factors:

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

mb_sample_id local_sample_id Diet Diet Genotype
SA427571KP_5155_Bl_C_KP_ControlControl KP
SA427572KP_5020_Bl_C_KP_ControlControl KP
SA427573KP_5021_Bl_C_KP_ControlControl KP
SA427574KP_5022_Bl_C_KP_ControlControl KP
SA427575KP_5156_Bl_C_KP_ControlControl KP
SA427576AAK_4896_Bl_C__PGKP_ControlControl PGKP
SA427577AAK_4900_Bl_C_PGKP_ControlControl PGKP
SA427578AAK_5013_Bl_C_PGKP_ControlControl PGKP
SA427579AAK_5005_Bl_C_PGKP_ControlControl PGKP
SA427580AAK_5004_Bl_C_PGKP_ControlControl PGKP
SA427581AAK_4942_Bl_C_PGKP_ControlControl PGKP
SA427582AAK_4898_Bl_C_PGKP_ControlControl PGKP
SA427583AA_4996_Bl_C_PolG_ControlControl PolG
SA427584AA_4997_Bl_C_PolG_ControlControl PolG
SA427585AA_5098_Bl_C_PolG_ControlControl PolG
SA427586AA_4894_Bl_C_PolG_ControlControl PolG
SA427587AA_4946_Bl_C_PolG_ControlControl PolG
SA427588AA_4993_Bl_C_PolG_ControlControl PolG
SA427589wt_5106_Bl_C_wt_ControlControl wt
SA427590wt_5018_Bl_C_wt_ControlControl wt
SA427591wt_5019_Bl_C_wt_ControlControl wt
SA427592wt_5015_Bl_C_wt_ControlControl wt
SA427593wt_5017_Bl_C_wt_ControlControl wt
SA427594KP_3430_Bl_woSG_KP_Ser/Gly freeSer/Gly free KP
SA427595KP_5167_Bl_woSG_KP_Ser/Gly freeSer/Gly free KP
SA427596KP_5169_Bl_woSG_KP_Ser/Gly freeSer/Gly free KP
SA427597KP_3327_Bl_woSG_KP_Ser/Gly freeSer/Gly free KP
SA427598KP_3370_Bl_woSG_KP_Ser/Gly freeSer/Gly free KP
SA427599KP_3371_Bl_woSG_KP_Ser/Gly freeSer/Gly free KP
SA427600KP_3425_Bl_woSG_KP_Ser/Gly freeSer/Gly free KP
SA427601AAK_5359_Bl_woSG_PGKP_Ser/Gly freeSer/Gly free PGKP
SA427602AAK_4992_Bl_woSG_PGKP_Ser/Gly freeSer/Gly free PGKP
SA427603AAK_4891_Bl_woSG_PGKP_Ser/Gly freeSer/Gly free PGKP
SA427604AAK_4840_Bl_woSG_PGKP_Ser/Gly freeSer/Gly free PGKP
SA427605AAK_4838_Bl_woSG_PGKP_Ser/Gly freeSer/Gly free PGKP
SA427606AAK_4837_Bl_woSG_PGKP_Ser/Gly freeSer/Gly free PGKP
SA427607AAK_4835_Bl_woSG_PGKP_Ser/Gly freeSer/Gly free PGKP
SA427608AAK_4830_Bl_woSG_PGKP_Ser/Gly freeSer/Gly free PGKP
SA427609AA_4829_Bl_woSG_PolG_Ser/Gly freeSer/Gly free PolG
SA427610AA_4891_Bl_woSG_PolG_Ser/Gly freeSer/Gly free PolG
SA427611AA_4954_Bl_woSG_PolG_Ser/Gly freeSer/Gly free PolG
SA427612AA_4984_Bl_woSG_PolG_Ser/Gly freeSer/Gly free PolG
SA427613AA_5009_Bl_woSG_PolG_Ser/Gly freeSer/Gly free PolG
SA427614AA_4828_Bl_woSG_PolG_Ser/Gly freeSer/Gly free PolG
SA427615wt_5103_Bl_woSG_wt_Ser/Gly freeSer/Gly free wt
SA427616wt_5104_Bl_woSG_wt_Ser/Gly freeSer/Gly free wt
SA427617wt_5105_Bl_woSG_wt_Ser/Gly freeSer/Gly free wt
SA427618wt_5107_Bl_woSG_wt_Ser/Gly freeSer/Gly free wt
SA427619wt_5108_Bl_woSG_wt_Ser/Gly freeSer/Gly free wt
SA427620wt_5109_Bl_woSG_wt_Ser/Gly freeSer/Gly free wt
SA427621wt_6542_Bl_woSG_wt_Ser/Gly freeSer/Gly free wt
Showing results 1 to 51 of 51

Collection:

Collection ID:CO004019
Collection Summary:Extraction of polar metabolites from plasma:To extract polar metabolites from mouse plasma 40 µL of cold methanol was added to a 15 µL of mouse plasma in a 1.5 mL microtube. This mixture was vortexed for 10 seconds and incubated for 20 minutes in a -20° C freezer. Samples were centrifuged for 10 min at 16,000g at 4° C. Next, supernatant A was collected in a new tube, and the pellet was saved for re-extraction. For re-extraction, the pellet was resuspended in 200 µL of 40:40:20 buffer, vortexed, and allowed to sit on ice for 10 min. The samples were centrifuged for 10 min at 16,000 g at 4° C. Supernatant B was collected and mixed with supernatant A. This mixture was further processed to remove phospholipids using 1 mL Phenomenex (Phenomenex Inc.) tubes according to the manufacturer's instruction and stored at -80° C until analysis by LC-MS.
Sample Type:Blood (plasma)
Volumeoramount Collected:1mL of organic phase of metabolites extraction
Storage Conditions:-80℃
Collection Vials:1.5 mL Eppendorf tubes
Storage Vials:1.5 mL Eppendorf tubes

Treatment:

Treatment ID:TR004035
Treatment Summary:Plasma were collected from animals with and without NSCLC

Sample Preparation:

Sampleprep ID:SP004032
Sampleprep Summary:Extraction of polar metabolites from plasma:To extract polar metabolites from mouse plasma 40 µL of cold methanol was added to a 15 µL of mouse plasma in a 1.5 mL microtube. This mixture was vortexed for 10 seconds and incubated for 20 minutes in a -20° C freezer. Samples were centrifuged for 10 min at 16,000g at 4° C. Next, supernatant A was collected in a new tube, and the pellet was saved for re-extraction. For re-extraction, the pellet was resuspended in 200 µL of 40:40:20 buffer, vortexed, and allowed to sit on ice for 10 min. The samples were centrifuged for 10 min at 16,000 g at 4° C. Supernatant B was collected and mixed with supernatant A. This mixture was further processed to remove phospholipids using 1 mL Phenomenex (Phenomenex Inc.) tubes according to the manufacturer's instruction and stored at -80° C until analysis by LC-MS.

Combined analysis:

Analysis ID AN006392 AN006393
Chromatography ID CH004846 CH004846
MS ID MS006093 MS006094
Analysis type MS MS
Chromatography type HILIC HILIC
Chromatography system Thermo Vanquish Thermo Vanquish
Column Waters XBridge BEH Amide (150 × 2.1mm, 2.5um) Waters XBridge BEH Amide (150 × 2.1mm, 2.5um)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Plus Orbitrap Thermo Q Exactive Plus Orbitrap
Ion Mode POSITIVE NEGATIVE
Units ion count ion count

Chromatography:

Chromatography ID:CH004846
Chromatography Summary:Plasma
Methods Filename:Chromatography_method.pdf
Instrument Name:Thermo Vanquish
Column Name:Waters XBridge BEH Amide (150 × 2.1mm, 2.5um)
Column Temperature:25 °C
Flow Gradient:0 min, 100% B; 3 min, 100% B; 3.2 min, 90% B; 6.2 min, 90% B; 6.5 min, 80% B; 10.5 min, 80% B; 10.7 min, 70% B; 13.5 min, 70% B; 13.7 min, 45% B; 16 min, 45% B; 16.5 min, 100% B; and 22 min, 100% B
Flow Rate:300 μL/min
Solvent A:95% water/5% acetonitrile; 20mM acetic acid; 40mM ammonium hydroxide (pH 9.4)
Solvent B:20% water/80% acetonitrile; 20mM acetic acid, 40mM ammonium hydroxide (pH 9.4)
Chromatography Type:HILIC

MS:

MS ID:MS006093
Analysis ID:AN006392
Instrument Name:Thermo Q Exactive Plus Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Maven
Ion Mode:POSITIVE
  
MS ID:MS006094
Analysis ID:AN006393
Instrument Name:Thermo Q Exactive Plus Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Maven
Ion Mode:NEGATIVE
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