Summary of Study ST003885

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.

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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 IDST003885
Study TitleRespiration defects limit serine synthesis required for lung cancer growth and survival - Effect of Polg mutation in NSCLC tumor derived lines (TDCLs)
Study SummaryThis study investigates the impact of mtDNA mutation burden induced by the PolGD256A mutation in NSCLC. Using in vitro models (TDCLs), we characterized we collected conditioned medium to mesure glucose and serine consumption. Here we found that mitochondria impairment cause more use of glucose and less use of serine from the culture medium. KP: NSCLC TDCLs generated from conditional animals PGKP: NSCLC TDCLs generated from conditional animals bearing PolG mutation
Institute
Rutgers University
DepartmentRutgers Cancer Institute
LaboratoryEileen White
Last NameCararo Lopes
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 Cararo Lopes Eduardo Cararo Lopes
https://dx.doi.org/10.21228/M8RN89
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

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:SU004020
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 Conditioned media Conditioned media Genotype
SA427190FM_3_Fresh Media_NoNo Fresh Media
SA427191FM_2_Fresh Media_NoNo Fresh Media
SA427192M11_2_KP_YesYes KP
SA427193M13_3_KP_YesYes KP
SA427194M11_3_KP_YesYes KP
SA427195M11_1_KP_YesYes KP
SA427196M14_2_KP_YesYes KP
SA427197M14_1_KP_YesYes KP
SA427198M14_3_KP_YesYes KP
SA427199M13_2_KP_YesYes KP
SA427200M13_1_KP_YesYes KP
SA427201M12_3_KP_YesYes KP
SA427202M12_2_KP_YesYes KP
SA427203M12_1_KP_YesYes KP
SA427204M44_3_PGKP_YesYes PGKP
SA427205M64_3_PGKP_YesYes PGKP
SA427206M64_2_PGKP_YesYes PGKP
SA427207M64_1_PGKP_YesYes PGKP
SA427208M63_3_PGKP_YesYes PGKP
SA427209M62_1_PGKP_YesYes PGKP
SA427210M61_3_PGKP_YesYes PGKP
SA427211M61_2_PGKP_YesYes PGKP
SA427212M61_1_PGKP_YesYes PGKP
SA427213M42_3_PGKP_YesYes PGKP
SA427214M44_2_PGKP_YesYes PGKP
SA427215M44_1_PGKP_YesYes PGKP
SA427216M43_3_PGKP_YesYes PGKP
SA427217M43_2_PGKP_YesYes PGKP
SA427218M43_1_PGKP_YesYes PGKP
SA427219M42_2_PGKP_YesYes PGKP
SA427220M41_3_PGKP_YesYes PGKP
SA427221M41_2_PGKP_YesYes PGKP
SA427222M41_1_PGKP_YesYes PGKP
SA427223M42_1_PGKP_YesYes PGKP
Showing results 1 to 34 of 34

Collection:

Collection ID:CO004013
Collection Summary:To determine the absolute concentrations of glucose and serine in the culture medium, we extracted metabolites from both fresh medium and conditioned medium after 72 hours of exposure to KP and PGKP TDCLs.
Sample Type:Culture Media
Volumeoramount Collected:400uL 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:TR004029
Treatment Summary:Conditioned culture media exposed to 72h of PGKP and KP TDCLs.

Sample Preparation:

Sampleprep ID:SP004026
Sampleprep Summary:Conditioned culture media exposed to 72h of PGKP and KP TDCLs. The analyses presented in this study were performed using the conditioned medium derived from the cell culture described in study 5752. The objective was to identify metabolites synthesized from glucose in the culture medium. In the table, where the genotype of the samples is specified as “Fresh medium,” it refers to unconditioned culture medium (not exposed to cells), which serves as a baseline for metabolite analysis of the conditioned medium from KP and PGKP TDCLs.

Chromatography:

Chromatography ID:CH004840
Chromatography Summary:Conditioned medium from NSCLC TDCLs.
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

Analysis:

Analysis ID:AN006381
Analysis Type:MS
Chromatography ID:CH004840
Num Factors:3
Num Metabolites:75
Rt Units:Minutes
Units:Ion counts
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