Summary of Study ST002435
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 PR001567. The data can be accessed directly via it's Project DOI: 10.21228/M84X5B 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.
| Study ID | ST002435 |
| Study Title | Metabolomics analysis of plasma from CHCHD10S59L/+ KI mice |
| Study Summary | Mutations in the coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) gene have been associated with a large clinical spectrum including myopathy, cardiomyopathy and amyotrophic lateral sclerosis (ALS). Herein, we analyzed the metabolic changes induced by the p.S59L CHCHD10 mutation to identify new therapeutic opportunities. Using metabolomic, lipidomic and proteomic analysis we observed a strong alteration of metabolism in plasma and heart of Chchd10S59L/+ mice compared to their wild type littermates at pre-symptomatic and symptomatic stages. In plasma, levels of phospholipids were decreased while those of carnitine derivatives and most of amino acids were increased. The cardiac tissue from Chchd10S59L/+ mice showed a decreased Oxidative Phosphorylation (OXPHOS) and β-oxidation proteins levels as well as tricarboxylic acid cycle (TCA) intermediates and carnitine pathway metabolism. In parallel, lipidomics analysis reveals a drastic change in the lipidome, including triglyceride, cardiolipin and phospholipids. Consistent with this energetic deficiency in cardiac tissue, we show that L-acetylcarnitine supplementation improves the mitochondrial network length in IPS-derived cardiomyocytes from a patient carrying the CHCHD10S59L/+ mutation. These data indicate that a bioenergetic intermediate such as L-acetylcarnitine may restore mitochondrial function in CHCHD10-related disease, due to the reduction in energy deficit that could be compensated by carnitine metabolic pathways. |
| Institute | INSERM |
| Last Name | Madji Hounoum |
| First Name | Blandine |
| Address | 151 Route Saint Antoine de Genistière 06204 Nice |
| madjihounoum@yahoo.fr | |
| Phone | +33 (0)4 89 06 43 01 |
| Submit Date | 2022-12-03 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzXML |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-12-04 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001567 |
| Project DOI: | doi: 10.21228/M84X5B |
| Project Title: | Multiomics study of CHCHD10S59L-related disease reveals energy metabolism downregulation: OXPHOS and β-oxidation deficiencies associated with lipids alterations |
| Project Summary: | Mutations in the coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) gene have been associated with a large clinical spectrum including myopathy, cardiomyopathy and amyotrophic lateral sclerosis (ALS). Herein, we analyzed the metabolic changes induced by the p.S59L CHCHD10 mutation to identify new therapeutic opportunities. Using metabolomic, lipidomic and proteomic analysis we observed a strong alteration of metabolism in plasma and heart of Chchd10S59L/+ mice compared to their wild type littermates at pre-symptomatic and symptomatic stages. In plasma, levels of phospholipids were decreased while those of carnitine derivatives and most of amino acids were increased. The cardiac tissue from Chchd10S59L/+ mice showed a decreased Oxidative Phosphorylation (OXPHOS) and ß-oxidation proteins levels as well as tricarboxylic acid cycle (TCA) intermediates and carnitine pathway metabolism. In parallel, lipidomics analysis reveals a drastic change in the lipidome, including triglyceride, cardiolipin and phospholipids. Consistent with this energetic deficiency in cardiac tissue, we show that L-acetylcarnitine supplementation improves the mitochondrial network length in IPS-derived cardiomyocytes from a patient carrying the CHCHD10S59L/+ mutation. These data indicate that a bioenergetic intermediate such as L-acetylcarnitine may restore mitochondrial function in CHCHD10-related disease, due to the reduction in energy deficit that could be compensated by carnitine metabolic pathways. |
| Institute: | INSERM |
| Department: | C3M |
| Laboratory: | RICCI |
| Last Name: | Madji Hounoum |
| First Name: | Blandine |
| Address: | 151 Route Saint Antoine de Genistière 06204 Nice |
| Email: | madjihounoum@yahoo.fr |
| Phone: | +33 (0)4 89 06 43 01 |
Subject:
| Subject ID: | SU002524 |
| 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 | Gender | Stage |
|---|---|---|---|---|
| SA243411 | Plasma_2017 | CHCHD10S59L/+ | female | Pre-symptomatic |
| SA243412 | Plasma_2016 | CHCHD10S59L/+ | female | Pre-symptomatic |
| SA243413 | Plasma_2012 | CHCHD10S59L/+ | female | Pre-symptomatic |
| SA243414 | Plasma_2025 | CHCHD10S59L/+ | female | Pre-symptomatic |
| SA243415 | Plasma_2768 | CHCHD10S59L/+ | female | Symptomatic |
| SA243416 | Plasma_1675 | CHCHD10S59L/+ | female | Symptomatic |
| SA243417 | Plasma_2769 | CHCHD10S59L/+ | female | Symptomatic |
| SA243406 | Plasma_2801 | CHCHD10S59L/+ | Male | Pre-symptomatic |
| SA243407 | Plasma_2021 | CHCHD10S59L/+ | Male | Symptomatic |
| SA243408 | Plasma_2010 | CHCHD10S59L/+ | Male | Symptomatic |
| SA243409 | Plasma_2009 | CHCHD10S59L/+ | Male | Symptomatic |
| SA243410 | Plasma_2007 | CHCHD10S59L/+ | Male | Symptomatic |
| SA243418 | Plasma_QC4 | QC | QC | QC |
| SA243419 | Plasma_QC3 | QC | QC | QC |
| SA243420 | Plasma_QC1 | QC | QC | QC |
| SA243421 | Plasma_QC2 | QC | QC | QC |
| SA243427 | Plasma_2024 | Wild-type | female | Pre-symptomatic |
| SA243428 | Plasma_2015 | Wild-type | female | Pre-symptomatic |
| SA243429 | Plasma_2027 | Wild-type | female | Pre-symptomatic |
| SA243430 | Plasma_2014 | Wild-type | female | Pre-symptomatic |
| SA243431 | Plasma_1674 | Wild-type | female | Symptomatic |
| SA243432 | Plasma_2773 | Wild-type | female | Symptomatic |
| SA243433 | Plasma_2772 | Wild-type | female | Symptomatic |
| SA243422 | Plasma_2800 | Wild-type | Male | Pre-symptomatic |
| SA243423 | Plasma_2008 | Wild-type | Male | Symptomatic |
| SA243424 | Plasma_2020 | Wild-type | Male | Symptomatic |
| SA243425 | Plasma_2018 | Wild-type | Male | Symptomatic |
| SA243426 | Plasma_2019 | Wild-type | Male | Symptomatic |
| Showing results 1 to 28 of 28 |
Collection:
| Collection ID: | CO002517 |
| Collection Summary: | Blood was taken by cardiac puncture from mice at pre-symptomatic (16 to 20 weeks of ages, n=5 mice per group) and symptomatic (40 to 48 weeks of ages, n=7 mice per group) stages, and transferred to EDTA coated tubes (Sarstedt). Then, blood was centrifuged at 500 rpm for 10 min at 4°C, plasma was collected and immediately frozen in microtubes (Eppendorf) and stored at −80°C until further analyses |
| Sample Type: | Blood (plasma) |
| Storage Conditions: | -80℃ |
Treatment:
| Treatment ID: | TR002536 |
| Treatment Summary: | Then, blood was centrifuged at 500 rpm for 10 min at 4°C, plasma was collected and immediately frozen in microtubes (Eppendorf) and stored at −80°C until further analyses |
Sample Preparation:
| Sampleprep ID: | SP002530 |
| Sampleprep Summary: | 20 µL were precipitated with methanol and centrifuged at 16 000 x g for 10 mins at 4°C, and the supernatant was dried |
| Processing Storage Conditions: | 4℃ |
| Extract Storage: | -80℃ |
Combined analysis:
| Analysis ID | AN003967 | AN003968 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | HILIC | Reversed phase |
| Chromatography system | Thermo Dionex Ultimate 3000 | Thermo Dionex Ultimate 3000 |
| Column | Phenomenex Kinetex HILIC 100A (50 x 2.1 mm, 2.6um) | Phenomenex Kinetex XB-C18 (150 x 2.1mm,1.7um) |
| MS Type | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap |
| MS instrument name | Thermo Q Exactive Plus Orbitrap | Thermo Q Exactive Plus Orbitrap |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | Relative units | Relative units |
Chromatography:
| Chromatography ID: | CH002933 |
| Instrument Name: | Thermo Dionex Ultimate 3000 |
| Column Name: | Phenomenex Kinetex HILIC 100A (50 x 2.1 mm, 2.6um) |
| Column Temperature: | 55°C |
| Flow Gradient: | 20 minutes |
| Flow Rate: | 0.4 mL/min |
| Solvent A: | Water |
| Solvent B: | Methanol |
| Chromatography Type: | HILIC |
| Chromatography ID: | CH002934 |
| Instrument Name: | Thermo Dionex Ultimate 3000 |
| Column Name: | Phenomenex Kinetex XB-C18 (150 x 2.1mm,1.7um) |
| Column Temperature: | 55°C |
| Flow Gradient: | 20 minutes |
| Flow Rate: | 0.4 mL/min |
| Solvent A: | Water |
| Solvent B: | ACN |
| Chromatography Type: | Reversed phase |
MS:
| MS ID: | MS003701 |
| Analysis ID: | AN003967 |
| Instrument Name: | Thermo Q Exactive Plus Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | The full-scan acquisition ranged from 58 to 870 m/z, the instrument operated at 70,000 resolution (m/z = 200).A targeted analysis was applied on the samples, based on a library of standard compounds (Mass Spectroscopy Metabolite Library (MSML®) of standards, IROA Technologies™). The following criteria were followed to identify the metabolites: (1) retention time of the detected metabolite within ± 20 s of the standard reference, (2) exact measured of molecular mass of the metabolite within a range of 10 ppm around the known molecular mass of the reference compound, and (3) correspondence between isotopic ratios of the metabolite and the standard reference. The signal value was calculated using Xcalibur® software (Thermo Fisher Scientific, San Jose, CA) by integrating the chromatographic peak area corresponding to the selected metabolite. |
| Ion Mode: | POSITIVE |
| MS ID: | MS003702 |
| Analysis ID: | AN003968 |
| Instrument Name: | Thermo Q Exactive Plus Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | The full-scan acquisition ranged from 58 to 870 m/z, the instrument operated at 70,000 resolution (m/z = 200).A targeted analysis was applied on the samples, based on a library of standard compounds (Mass Spectroscopy Metabolite Library (MSML®) of standards, IROA Technologies™). The following criteria were followed to identify the metabolites: (1) retention time of the detected metabolite within ± 20 s of the standard reference, (2) exact measured of molecular mass of the metabolite within a range of 10 ppm around the known molecular mass of the reference compound, and (3) correspondence between isotopic ratios of the metabolite and the standard reference. The signal value was calculated using Xcalibur® software (Thermo Fisher Scientific, San Jose, CA) by integrating the chromatographic peak area corresponding to the selected metabolite. |
| Ion Mode: | NEGATIVE |
