Summary of Study ST003766
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 PR002349. The data can be accessed directly via it's Project DOI: 10.21228/M80N9V This work is supported by NIH grant, U2C- DK119886. See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST003766 |
| Study Title | Hepatic bioenergetics and metabolism in mitochondrial disease: Insights from the Ndufs4 KO mouse model |
| Study Type | Multi-platform metabolomics analysis |
| Study Summary | Mitochondrial diseases, including Leigh syndrome, frequently result from complex I (CI) deficiencies and lack effective treatments. Investigating metabolic alterations in affected tissues is essential to understanding disease progression and identifying therapeutic targets. The aim of this project was to characterize the metabolic profile of Ndufs4 knockout (KO) mouse livers, a model of CI deficiency, using multi-platform metabolomics. Whole-liver extracts from Ndufs4 KO and wild-type mice were analyzed via untargeted GC-TOFMS and semi-targeted LC-MS/MS. Metabolic profiling revealed widespread disruptions, including altered glucose, amino acid, and nucleotide metabolism, as well as TCA cycle intermediates. Key findings included elevated levels of UDP-glucose and UDP-N-acetylglucosamine, indicating shifts toward anabolic pathways such as hexosamine biosynthesis and glycogen synthesis. These data highlight the potential role of metabolic reprogramming in liver adaptation to mitochondrial dysfunction and provide new directions for investigating interorgan metabolic dynamics in mitochondrial diseases. |
| Institute | North-West University |
| Department | Biochemistry |
| Laboratory | Mitochondria Research Group |
| Last Name | Louw |
| First Name | Roan |
| Address | Hoffman Street, Potchefstroom, North-West, 2520, South Africa |
| Roan.Louw@nwu.ac.za | |
| Phone | +27 18 299 4074 |
| Submit Date | 2024-12-02 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | smp, d |
| Analysis Type Detail | GC-MS/LC-MS |
| Release Date | 2025-12-02 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002349 |
| Project DOI: | doi: 10.21228/M80N9V |
| Project Title: | Metabolomics of Ndufs4 KO liver |
| Project Type: | Multi-platform metabolomics analysis |
| Project Summary: | Mitochondrial diseases, including Leigh syndrome, frequently result from complex I (CI) deficiencies and lack effective treatments. Investigating metabolic alterations in affected tissues is essential to understanding disease progression and identifying therapeutic targets. The aim of this project was to characterize the metabolic profile of Ndufs4 knockout (KO) mouse livers, a model of CI deficiency, using multi-platform metabolomics. Whole-liver extracts from Ndufs4 KO and wild-type mice were analyzed via untargeted GC-TOFMS and semi-targeted LC-MS/MS. Metabolic profiling revealed widespread disruptions, including altered glucose, amino acid, and nucleotide metabolism, as well as TCA cycle intermediates. Key findings included elevated levels of UDP-glucose and UDP-N-acetylglucosamine, indicating shifts toward anabolic pathways such as hexosamine biosynthesis and glycogen synthesis. These data highlight the potential role of metabolic reprogramming in liver adaptation to mitochondrial dysfunction and provide new directions for investigating interorgan metabolic dynamics in mitochondrial diseases. |
| Institute: | North-West University |
| Department: | Biochemistry |
| Laboratory: | Mitochondria Research Group |
| Last Name: | Louw |
| First Name: | Roan |
| Address: | Hoffman Street, Potchefstroom, North-West, 2520, South Africa |
| Email: | Roan.Louw@nwu.ac.za |
| Phone: | +27 18 299 4074 |
Subject:
| Subject ID: | SU003899 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Genotype Strain: | Ndufs4, https://www.jax.org/strain/027058 |
| Gender: | Male |
| Animal Animal Supplier: | Jackson Laboratory (ME, USA) |
| Animal Light Cycle: | 12:12 h |
| Animal Feed: | Rodent Breeder, Cat. #RM1845, LabChef, Nutritionhub |
| Animal Water: | ad libitum |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Genotype |
|---|---|---|
| SA409493 | 22L | KO |
| SA409494 | 6L | KO |
| SA409495 | 12L | KO |
| SA409496 | 14L | KO |
| SA409497 | 15L | KO |
| SA409498 | 16L | KO |
| SA409499 | 19L | KO |
| SA409500 | 21L | KO |
| SA409501 | 23L | KO |
| SA409502 | 4L | KO |
| SA409503 | 27L | KO |
| SA409504 | 31L | KO |
| SA409505 | 33L | KO |
| SA409506 | 34L | KO |
| SA409507 | 35L | KO |
| SA409508 | 39L | KO |
| SA409509 | 40L | KO |
| SA409510 | 5L | KO |
| SA409511 | 1L | KO |
| SA409512 | 3L | WT |
| SA409513 | 18L | WT |
| SA409514 | 7L | WT |
| SA409515 | 8L | WT |
| SA409516 | 9L | WT |
| SA409517 | 10L | WT |
| SA409518 | 11L | WT |
| SA409519 | 13L | WT |
| SA409520 | 17L | WT |
| SA409521 | 20L | WT |
| SA409522 | 38L | WT |
| SA409523 | 24L | WT |
| SA409524 | 25L | WT |
| SA409525 | 26L | WT |
| SA409526 | 28L | WT |
| SA409527 | 29L | WT |
| SA409528 | 32L | WT |
| SA409529 | 36L | WT |
| SA409530 | 37L | WT |
| SA409531 | 2L | WT |
| Showing results 1 to 39 of 39 |
Collection:
| Collection ID: | CO003892 |
| Collection Summary: | Mice were euthanized between postnatal day (P) 45-50 via cervical dislocation at the same time of day (8:00-9:00 AM) after overnight (12-h) fasting. The liver was removed, snap-frozen in liquid nitrogen, and stored at −80°C until used. |
| Sample Type: | Liver |
| Storage Conditions: | -80℃ |
Treatment:
| Treatment ID: | TR003908 |
| Treatment Summary: | The animals did not receive any treatment. |
Sample Preparation:
| Sampleprep ID: | SP003905 |
| Sampleprep Summary: | Metabolite extraction was achieved using a modified monophasic Bligh–Dyer extraction method with a solvent ratio of 3:1:1 (methanol:water:chloroform). The water used during extraction contained internal standards. |
Combined analysis:
| Analysis ID | AN006181 | AN006182 |
|---|---|---|
| Chromatography ID | CH004692 | CH004693 |
| MS ID | MS005885 | MS005886 |
| Analysis type | MS | MS |
| Chromatography type | Reversed phase | GC |
| Chromatography system | Agilent 1260 infinity | Agilent 7890A |
| Column | Agilent ZORBAX RRHT StableBond Aq (100 x 2.1mm, 1.8um) | Restek Rxi-5MS (28.6m x 0.25mm,0.25um) |
| MS Type | ESI | EI |
| MS instrument type | Triple quadrupole | GC-TOF |
| MS instrument name | Agilent 6470 | Leco Pegasus HT TOF |
| Ion Mode | POSITIVE | POSITIVE |
| Units | Normalised peak areas |
Chromatography:
| Chromatography ID: | CH004692 |
| Chromatography Summary: | ZORBAX RRHT StableBond Aq Column (Part Number:828700-914) |
| Instrument Name: | Agilent 1260 infinity |
| Column Name: | Agilent ZORBAX RRHT StableBond Aq (100 x 2.1mm, 1.8um) |
| Column Temperature: | 45 |
| Flow Gradient: | 95 % of solvent A held for 0.2 min, increased to 25 % of solvent B over 1.8 min, held for 5 min, increased to 90 % of solvent B over 0.5 min, held for 1.6 min, increased to 95 % of solvent B over 2.9 min, decreased to 5 % of solvent B over 1 min, and re-equilibrated for 3 min to give a total run time of 16 min. |
| Flow Rate: | For the first 9 min of the run, the mobile phase flow rate was set at 0.3 mL/min, after which it was increased to 0.4 mL/min in a span of 0.1 min and maintained at this level for the subsequent 3.9 min of the run |
| Sample Injection: | One microliter of each sample was injected |
| Solvent A: | 100% water; 0.1 % formic acid |
| Solvent B: | 100% acetonitrile; 0.1 % formic acid |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH004693 |
| Instrument Name: | Agilent 7890A |
| Column Name: | Restek Rxi-5MS (28.6m x 0.25mm,0.25um) |
| Column Temperature: | 70°C for 1 min, 7°C/min minute increase until 120°C, 10°C/min increase until 230°C, 13°C/min increase until 300°C, held for 1 min |
| Flow Gradient: | - |
| Flow Rate: | - |
| Solvent A: | - |
| Solvent B: | - |
| Chromatography Type: | GC |
MS:
| MS ID: | MS005885 |
| Analysis ID: | AN006181 |
| Instrument Name: | Agilent 6470 |
| Instrument Type: | Triple quadrupole |
| MS Type: | ESI |
| MS Comments: | Amino acid and acylcarnitine species were analyzed by dynamic multiple reaction monitoring of the transition from precursor to product ions at associated optimized collision energies, and fragmentor voltages using Agilent Masshunter. |
| Ion Mode: | POSITIVE |
| MS ID: | MS005886 |
| Analysis ID: | AN006182 |
| Instrument Name: | Leco Pegasus HT TOF |
| Instrument Type: | GC-TOF |
| MS Type: | EI |
| MS Comments: | After a solvent delay of 250 seconds, data were gathered at a rate of 20 spectra per second, employing a mass-to-charge (m/z) ratio scan range spanning from 50 to 950 amu. |
| Ion Mode: | POSITIVE |
