Summary of Study ST002315

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.

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 IDST002315
Study TitleDifferential requirements for mitochondrial electron transport chain components in the adult murine liver - in vivo glucose tracing
Study SummaryWild-type and knockout mice (Ndufa9 and Cox10) were implanted with a jugular vein catheter and infused with [U-13C] glucose for 3 hours. Plasma and liver tissue was collected and analyzed via GCMS.
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 Date2022-08-23
Num Groups8
Total Subjects60
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

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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:SU002401
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
SA227161XW37N_plasma_0hCox10_KO
SA227162XW36N_plasma_4hCox10_KO
SA227163XW36N_plasma_3hCox10_KO
SA227164XW36N_plasma_1hCox10_KO
SA227165XW37N_plasma_3hCox10_KO
SA227166XW72L_plasma_3hCox10_KO
SA227167XW72L_plasma_0hCox10_KO
SA227168XW36N_liverCox10_KO
SA227169XW72L_plasma_1hCox10_KO
SA227170XW36N_plasma_0hCox10_KO
SA227171XW37N_plasma_4hCox10_KO
SA227172XW37N_plasma_1hCox10_KO
SA227173XW37N_liverCox10_KO
SA227174XW72L_plasma_4hCox10_KO
SA227175XW72L_liverCox10_KO
SA227176XW37B_plasma_3hCox10_WT
SA227177XW37B_plasma_1hCox10_WT
SA227178XW37B_plasma_4hCox10_WT
SA227179XW37L_liverCox10_WT
SA227180XW37B_plasma_0hCox10_WT
SA227181XW37B_liverCox10_WT
SA227182XW73R_plasma_4hCox10_WT
SA227183XW37L_plasma_4hCox10_WT
SA227184XW73R_liverCox10_WT
SA227185XW73R_plasma_0hCox10_WT
SA227186XW73R_plasma_3hCox10_WT
SA227187XW73R_plasma_1hCox10_WT
SA227188XW37L_plasma_0hCox10_WT
SA227189XW37L_plasma_3hCox10_WT
SA227190XW37L_plasma_1hCox10_WT
SA227191XW51B_plasma_1hNdufa9_KO
SA227192XW51B_plasma_3hNdufa9_KO
SA227193XW51B_plasma_4hNdufa9_KO
SA227194XW51B_plasma_0hNdufa9_KO
SA227195XW51N_plasma_3hNdufa9_KO
SA227196XW51N_plasma_0hNdufa9_KO
SA227197XW51N_plasma_1hNdufa9_KO
SA227198XW51L_plasma_4hNdufa9_KO
SA227199XW51N_plasma_4hNdufa9_KO
SA227200XW51L_liverNdufa9_KO
SA227201XW51B_liverNdufa9_KO
SA227202XW51L_plasma_0hNdufa9_KO
SA227203XW51L_plasma_1hNdufa9_KO
SA227204XW51L_plasma_3hNdufa9_KO
SA227205XW51N_liverNdufa9_KO
SA227206XW71L_liverNdufa9_WT
SA227207XW71N_liverNdufa9_WT
SA227208XW71R_liverNdufa9_WT
SA227209XW71L_plasma_4hNdufa9_WT
SA227210XW71L_plasma_0hNdufa9_WT
SA227211XW71N_plasma_4hNdufa9_WT
SA227212XW71N_plasma_3hNdufa9_WT
SA227213XW71N_plasma_1hNdufa9_WT
SA227214XW71N_plasma_0hNdufa9_WT
SA227215XW71R_plasma_0hNdufa9_WT
SA227216XW71R_plasma_1hNdufa9_WT
SA227217XW71L_plasma_1hNdufa9_WT
SA227218XW71R_plasma_4hNdufa9_WT
SA227219XW71R_plasma_3hNdufa9_WT
SA227220XW71L_plasma_3hNdufa9_WT
Showing results 1 to 60 of 60

Collection:

Collection ID:CO002394
Collection Summary:Liver was frozen on liqN2. Liver was crushed on liqN2, and metabolites extracted with 80% meOH. Plasma was extracted by adding 10X cold acetone. MeOH was dried, and samples derivatized to form methoxime-TBDMS adducts and immediately injected onto the GCMS.
Sample Type:Liver

Treatment:

Treatment ID:TR002413
Treatment Summary:Mice were implanted with a jugular vein catheter. Conscious mice were infused with [U-13C] glucose for 4 hours.

Sample Preparation:

Sampleprep ID:SP002407
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 AN003782
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:CH002796
Chromatography Summary:60 °C for 1 min then 10 °C/min to 320 °C for 1 min Run Time 28 min 9 min (Post Run) 320 °C
Methods Filename:acqmeth_(1).txt
Instrument Name:Agilent 7890B
Column Name:Agilent HP5-MS (30m x 0.25mm, 0.25 um)
Flow Rate:104.48 mL/min
Injection Temperature:60
Internal Standard:Norvaline
Sample Injection:Splitless
Chromatography Type:GC

MS:

MS ID:MS003525
Analysis ID:AN003782
Instrument Name:Agilent 5977A
Instrument Type:Single quadrupole
MS Type:EI
MS Comments:MS scan from 75-1000 m/z Data processed using Agilent Enhanced Data Analysis Peaks were autointegrated and confirmed by hand.
Ion Mode:POSITIVE
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