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.

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.

Perform statistical analysis  |  Show all samples  |  Show named metabolites  |  Download named metabolite data  
Download mwTab file (text)   |  Download mwTab file(JSON)   |  Download data files (Contains raw data)
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
  logo