Summary of Study ST002434

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.

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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 IDST002434
Study TitleMetabolomics analysis of heart from CHCHD10S59L/+ KI mice
Study SummaryMutations 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 NameMadji Hounoum
First NameBlandine
Address151 Route Saint Antoine de Genistière 06204 NIce
Emailmadjihounoum@yahoo.fr
Phone+33 (0)4 89 06 43 01
Submit Date2022-12-03
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailLC-MS
Release Date2023-12-04
Release Version1
Blandine Madji Hounoum Blandine Madji Hounoum
https://dx.doi.org/10.21228/M84X5B
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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:SU002523
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Species Group:Mammals

Factors:

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

mb_sample_id local_sample_id Genotype Gender Stage
SA243385Heart_16CHCHD10S59L/+ female Symptomatic
SA243386Heart_17CHCHD10S59L/+ female Symptomatic
SA243387Heart_23CHCHD10S59L/+ female Symptomatic
SA243388Heart_22CHCHD10S59L/+ female Symptomatic
SA243377Heart_11CHCHD10S59L/+ Male Symptomatic
SA243378Heart_9CHCHD10S59L/+ Male Symptomatic
SA243379Heart_12CHCHD10S59L/+ Male Symptomatic
SA243380Heart_24CHCHD10S59L/+ Male Symptomatic
SA243381Heart_18CHCHD10S59L/+ Male Symptomatic
SA243382Heart_8CHCHD10S59L/+ Male Symptomatic
SA243383Heart_10CHCHD10S59L/+ Male Symptomatic
SA243384Heart_7CHCHD10S59L/+ Male Symptomatic
SA243389Heart_QC5QC QC QC
SA243390Heart_QC4QC QC QC
SA243391Heart_QC2QC QC QC
SA243392Heart_QC3QC QC QC
SA243393Heart_QC1QC QC QC
SA243402Heart_13Wild-type female Symptomatic
SA243403Heart_19Wild-type female Symptomatic
SA243404Heart_14Wild-type female Symptomatic
SA243405Heart_20Wild-type female Symptomatic
SA243394Heart_21Wild-type Male Symptomatic
SA243395Heart_15Wild-type Male Symptomatic
SA243396Heart_4Wild-type Male Symptomatic
SA243397Heart_6Wild-type Male Symptomatic
SA243398Heart_3Wild-type Male Symptomatic
SA243399Heart_1Wild-type Male Symptomatic
SA243400Heart_2Wild-type Male Symptomatic
SA243401Heart_5Wild-type Male Symptomatic
Showing results 1 to 29 of 29

Collection:

Collection ID:CO002516
Collection Summary:Cardiac tissue samples were immediately flash frozen in liquid nitrogen and stored at -80 °C until further analyses
Sample Type:Cardiac tissue
Storage Conditions:-80℃

Treatment:

Treatment ID:TR002535
Treatment Summary:NA

Sample Preparation:

Sampleprep ID:SP002529
Sampleprep Summary:Tissues were ground to powder by using liquid nitrogen cooled mortar and pestle. 11.1 mg of powder tissue were extracted with 1 mL cold acetonitrile/water (1:1, v/v). The suspension was vortexed, incubated at 4°C for 1 h, centrifuged at 16 000 x g for 10 mins at 4°C and then 450 µL of the supernatant was dried. For plasma metabolites extraction, 20 µL were precipitated with methanol and centrifuged at 16 000 x g for 10 mins at 4°C, and the supernatant was dried. All dried metabolites extract from tissues were reconstituted in 100 µL of either methanol/water (1: 9, v/v) or ACN/water (9: 1, v/v) depending on the LC-column used and 10 µL was injected into LC-HRMS system
Processing Storage Conditions:4℃
Extract Storage:-80℃

Chromatography:

Chromatography ID:CH002931
Instrument Name:Thermo Dionex Ultimate 3000
Column Name:Thermo Accucore HILIC (100 x 2.1mm, 2.6um)
Flow Gradient:20 minutes
Flow Rate:0.4 mL/min
Solvent A:Water
Solvent B:Methanol
Chromatography Type:HILIC
  
Chromatography ID:CH002932
Instrument Name:Thermo Dionex Ultimate 3000
Column Name:Phenomenex Kinetex C18 (150 x 2.1mm, 2.6 um)
Flow Gradient:20 minutes
Flow Rate:0.4 mL/min
Solvent A:Water
Solvent B:ACN
Chromatography Type:Reversed phase

Analysis:

Analysis ID:AN003964
Analysis Type:MS
Chromatography ID:CH002931
Num Factors:5
Num Metabolites:78
Rt Units:Minutes
Units:relative units
  
Analysis ID:AN003965
Analysis Type:MS
Chromatography ID:CH002932
Num Factors:5
Num Metabolites:92
Rt Units:Minutes
Units:relative units
  
Analysis ID:AN003966
Analysis Type:MS
Chromatography ID:CH002932
Num Factors:5
Num Metabolites:70
Rt Units:Minutes
Units:relative units
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