Summary of Study ST003883

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

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 IDST003883
Study TitleRespiration defects limit serine synthesis required for lung cancer growth and survival - Effect of Polg mutation in NSCLC Tissues
Study SummaryThis study investigates the impact of mtDNA mutation burden induced by the PolG D256A mutation in NSCLC. Using in vivo (GEMMs), we characterized the metabolic profile of NSCLC harboring this mutation compared to controls. Here, we show that PolG mutation causes mitochondrial dysfunction, impacting serine/glycine metabolism as well as energy metabolism through glycolysis. This study was conducted in animals divided into two age groups. The "young" group consisted of animals in which NSCLC was initiated at 3 months of age, while the "old" group included animals whose tumors were initiated at 10 months of age. WT: Wild Type animals KP: NSCLC conditional animals PolG: Animals with PolG mutation PGKP: NSCLC conditional animals with PolG mutation
Institute
Rutgers University
DepartmentRutgers Cancer Institute
LaboratoryEileen White
Last NameLopes
First NameEduardo
Address195 Little Albany Street
Emailedu.llopes@gmail.com
Phone732-235-5795
Submit Date2025-03-18
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:SU004018
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 Sample source Age Genotype
SA426863603__LungLung Old PolG
SA426864971__LungLung Old PolG
SA426865972__LungLung Old PolG
SA4268661191__LungLung Old PolG
SA4268671751__LungLung Old PolG
SA4268682819__LungLung Old PolG
SA4268692996__LungLung Old PolG
SA4268703273__LungLung Old PolG
SA4268716572__LungLung Old PolG
SA4268726578__LungLung Old PolG
SA4268736830__LungLung Old PolG
SA4268747170__LungLung Old PolG
SA4268759024__LungLung Old PolG
SA426876944__LungLung Old PolG
SA4269001021__LungLung Old Wt
SA426877574__LungLung Old WT
SA4268781310__LungLung Old WT
SA4268794818__LungLung Old WT
SA4268804817__LungLung Old WT
SA4268812740__LungLung Old WT
SA4268822395__LungLung Old WT
SA4268832394__LungLung Old WT
SA4268842378__LungLung Old WT
SA4268851311__LungLung Old WT
SA426886961__LungLung Old WT
SA426887330__LungLung Old WT
SA426888586__LungLung Old WT
SA426889585__LungLung Old WT
SA426890581__LungLung Old WT
SA4268918241__LungLung Old WT
SA4268926833__LungLung Old WT
SA4268936587__LungLung Old WT
SA4268946348__LungLung Old WT
SA426895577__LungLung Old WT
SA4268966347__LungLung Old WT
SA4268976216__LungLung Old WT
SA4268989986__LungLung Old WT
SA4268998244__LungLung Old WT
SA4269016373__LungLung Young PolG
SA4269026370__LungLung Young PolG
SA4269036212__LungLung Young PolG
SA4269046205__LungLung Young PolG
SA4269056203__LungLung Young PolG
SA4269065689__LungLung Young PolG
SA4269074896__LungLung Young PolG
SA4269084595__LungLung Young PolG
SA4269095200__LungLung Young PolG
SA4269102209__LungLung Young WT
SA4269114194__LungLung Young WT
SA4269122206__LungLung Young WT
SA4269136219__LungLung Young WT
SA4269146353__LungLung Young WT
SA4269156352__LungLung Young WT
SA4269166350__LungLung Young WT
SA4269176233__LungLung Young WT
SA4269186229__LungLung Young WT
SA4269196221__LungLung Young WT
SA4269204599__LungLung Young WT
SA4269216232__LungLung Young WT
SA4269226228__LungLung Young WT
SA4269234193__LungLung Young WT
SA4269246220__LungLung Young WT
SA4269256222__LungLung Young WT
SA4269266226__LungLung Young WT
SA4269276224__LungLung Young WT
SA426928255__PlasmaPlasma Old KP
SA4269296230__PlasmaPlasma Old KP
SA426930256__PlasmaPlasma Old KP
SA4269311002__PlasmaPlasma Old KP
SA4269321313__PlasmaPlasma Old KP
SA4269337468__PlasmaPlasma Old KP
SA4269348240__PlasmaPlasma Old KP
SA4269358967__PlasmaPlasma Old KP
SA4269368968__PlasmaPlasma Old KP
SA4269378969__PlasmaPlasma Old KP
SA4269381309__PlasmaPlasma Old KP
SA4269398970__PlasmaPlasma Old KP
SA4269401003__PlasmaPlasma Old KP
SA426941257__PlasmaPlasma Old KP
SA4269421312__PlasmaPlasma Old KP
SA4269439953__PlasmaPlasma Old PGKP
SA4269442411__PlasmaPlasma Old PGKP
SA4269459973__PlasmaPlasma Old PGKP
SA4269469968__PlasmaPlasma Old PGKP
SA4269479964__PlasmaPlasma Old PGKP
SA4269489962__PlasmaPlasma Old PGKP
SA4269498848__PlasmaPlasma Old PGKP
SA4269509979__PlasmaPlasma Old PGKP
SA426951971__PlasmaPlasma Old PolG
SA426952972__PlasmaPlasma Old PolG
SA4269531191__PlasmaPlasma Old PolG
SA4269541751__PlasmaPlasma Old PolG
SA4269552819__PlasmaPlasma Old PolG
SA426956603__PlasmaPlasma Old PolG
SA4269572996__PlasmaPlasma Old PolG
SA4269589024__PlasmaPlasma Old PolG
SA426959944__PlasmaPlasma Old PolG
SA426960577__PlasmaPlasma Old WT
SA4269619986__PlasmaPlasma Old WT
SA426962574__PlasmaPlasma Old WT
Showing page 1 of 3     Results:    1  2  3  Next     Showing results 1 to 100 of 219

Collection:

Collection ID:CO004011
Collection Summary:Extraction of polar metabolites from solid tissues: 20 to 30 mg of tissues were weighed and added to a 2 mL round-tipped microtube with a – 80° C cold Yttria Grinding Ball per tube. The tissues were pulverized in CryoMill (Retsch) following alternating three cycles at 5 Hz for 2 min with three cycles at 25 Hz for 2 min. Buffer was added to each 2 mL microtube (sample weight x 40)/2 volume of the buffer) 40:40:20 buffer with 0.5% formic acid, samples were vigorously vortexed and incubated on ice for 10 minutes, vortexed, and incubated for an additional 10 min. After the samples were centrifuged for 10 min at 16,000g at 4° C, the supernatant A was collected and saved, and the pellets were submitted to re-extraction following the same procedure to generate supernatant B. Supernatant A and B were mixed and transferred to a clean 1.5 mL microtube with the appropriated volume of 15% NH4CO3. The samples were stored in a -80° C freezer until analysis by LC-MS. 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. Ion counts table: The Ion Counts table (Peaks Extracted) includes the integrated data from all tissue types analyzed: plasma, tumor, and lung. Metabolites extracted from plasma are labeled as “MetaboliteX_Plasma,” whereas those from tumors or lungs are labeled simply as “MetaboliteX.”
Sample Type:Lung, Tumors, and 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:TR004027
Treatment Summary:Tumor or Lungs and Plasma were collected from animals with and without NSCLC.

Sample Preparation:

Sampleprep ID:SP004024
Sampleprep Summary:For Lung and Tumors: 20 to 30 mg of tissues were weighed and added to a 2 mL round-tipped microtube with a – 80° C cold Yttria Grinding Ball per tube. The tissues were pulverized in CryoMill (Retsch) following alternating three cycles at 5 Hz for 2 min with three cycles at 25 Hz for 2 min. Buffer was added to each 2 mL microtube (sample weight x 40)/2 volume of the buffer) 40:40:20 buffer with 0.5% formic acid, samples were vigorously vortexed and incubated on ice for 10 minutes, vortexed, and incubated for an additional 10 min. After the samples were centrifuged for 10 min at 16,000g at 4° C, the supernatant A was collected and saved, and the pellets were submitted to re-extraction following the same procedure to generate supernatant B. Supernatant A and B were mixed and transferred to a clean 1.5 mL microtube with the appropriated volume of 15% NH4CO3. The samples were stored in a -80° C freezer until analysis by LC-MS. For 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.

Chromatography:

Chromatography ID:CH004838
Chromatography Summary:Running method for Tumor, Lung and 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

Analysis:

Analysis ID:AN006377
Analysis Type:MS
Chromatography ID:CH004838
Num Factors:17
Num Metabolites:227
Units:ion count
  
Analysis ID:AN006378
Analysis Type:MS
Chromatography ID:CH004838
Num Factors:17
Num Metabolites:325
Units:ion count
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