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 |
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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℃ |
