Summary of Study ST002314

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 PR001484. The data can be accessed directly via it's Project DOI: 10.21228/M8WT54 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 IDST002314
Study TitleDifferential requirements for mitochondrial electron transport chain components in the adult murine liver - Lactate/Pyruvate Tolerance Test
Study SummaryHepatic Cox10 knockout mice were injected with a lactate/pyruvate (10:1) solution with 40% of the mixture labeled with [U-13C]. After 30 minutes, plasma and liver tissue was harvested. Metabolites were extracted, dried, and derivatized to form methoxime-TBDMS adducts.
Institute
The University of Texas Southwestern Medical Center at Dallas
DepartmentChildren's Research Institute
LaboratoryPrashant Mishra
Last NameLesner
First NameNicholas
Address6000 Harry Hines BLVD
Emailnicholas.lesner@pennmedicine.upenn.edu
Phone2146483784
Submit Date2022-08-22
Num Groups2
Total Subjects9
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailGC-MS
Release Date2022-11-02
Release Version1
Nicholas Lesner Nicholas Lesner
https://dx.doi.org/10.21228/M8WT54
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001484
Project DOI:doi: 10.21228/M8WT54
Project Title:Differential requirements for mitochondrial electron transport chain components in the adult murine liver
Project Summary:Mitochondrial electron transport chain (ETC) dysfunction due to mutations in the nuclear or mitochondrial genome is a common cause of metabolic disease in humans, and displays striking tissue specificity depending on the affected gene. The mechanisms underlying tissue specific phenotypes are not understood. Complex I (cI) is classically considered the entry point for electrons into the ETC, and in vitro experiments indicate that cI is required for basal respiration and maintenance of the NAD+/NADH ratio, an indicator of cellular redox status. This finding has largely not been tested in vivo. Here, we report that mitochondrial complex I (cI) is dispensable for homeostasis of the adult mouse liver; animals with hepatocyte-specific loss of cI function display no overt phenotypes or signs of liver damage, and maintain liver function, redox and oxygen status. Further analysis of cI-deficient livers did not reveal significant proteomic or metabolic changes, indicating little to no compensation is required in the setting of complex I loss. In contrast, complex IV (cIV) dysfunction in adult hepatocytes results in decreased liver function, impaired oxygen handling, steatosis, and liver damage, accompanied by significant metabolomic and proteomic perturbations. Metabolomic analysis suggests that the electron transfer flavoprotein complex constitutes a major route for electron entry into the hepatic ETC. Our results support a model whereby complex I loss is tolerated in the mouse liver because hepatocytes use alternative electron donors to fuel the mitochondrial ETC.
Institute:The University of Texas Southwestern Medical Center at Dallas
Department:Children's Research Institute
Laboratory:Prashant Mishra
Last Name:Lesner
First Name:Nicholas
Address:6000 Harry Hines BLVD
Email:nicholas.lesner@pennmedicine.upenn.edu
Phone:2146483784

Subject:

Subject ID:SU002400
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090

Factors:

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

mb_sample_id local_sample_id Genotype
SA227143283LKO
SA227144263R_plasmaKO
SA227145268N_plasmaKO
SA227146283RKO
SA227147264R_plasmaKO
SA227148283R_plasmaKO
SA227149283L_plasmaKO
SA227150263RKO
SA227151268NKO
SA227152264RKO
SA227153283N_plasmaWT
SA227154264L_plasmaWT
SA227155263N_plasmaWT
SA227156264NWT
SA227157264LWT
SA227158283NWT
SA227159263NWT
SA227160264N_plasmaWT
Showing results 1 to 18 of 18

Collection:

Collection ID:CO002393
Collection Summary:Liver was frozen on liqN2. Liver was crushed on liqN2, and metabolites extracted with 80% meOH. MeOH was dried, and samples derivatized to form methoxime-TBDMS adducts and immediately injected onto the GCMS.
Sample Type:Liver

Treatment:

Treatment ID:TR002412
Treatment Summary:Mice were IP injected with a lactate/pyruvate (10:1) solution.

Sample Preparation:

Sampleprep ID:SP002406
Sampleprep Summary:80% methanol containing metabolites was dried overnight in a speedvac. Dried pellets were derivatized using methoxyamine and MTBSTFA. Samples were immediately injected.

Combined analysis:

Analysis ID AN003781
Analysis type MS
Chromatography type GC
Chromatography system Agilent 7890B
Column Agilent HP5-MS (30m x 0.25mm, 0.25 um)
MS Type EI
MS instrument type Single quadrupole
MS instrument name Agilent 5977A
Ion Mode POSITIVE
Units peak area

Chromatography:

Chromatography ID:CH002795
Chromatography Summary:60C for 1 min then 10C/min to 320C for 1 min 9 min at 320C
Instrument Name:Agilent 7890B
Column Name:Agilent HP5-MS (30m x 0.25mm, 0.25 um)
Injection Temperature:60
Internal Standard:Norvaline
Sample Injection:Splitless
Chromatography Type:GC

MS:

MS ID:MS003524
Analysis ID:AN003781
Instrument Name:Agilent 5977A
Instrument Type:Single quadrupole
MS Type:EI
MS Comments:Scan 75 - 1000 m/z Data processed using Agilent Enhanced Data Analysis Peaks were auto integrated and confirmed by hand.
Ion Mode:POSITIVE
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