Summary of project PR001567
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
| 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 |
Summary of all studies in project PR001567
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002434 | Metabolomics analysis of heart from CHCHD10S59L/+ KI mice | Mus musculus | INSERM | MS | 2023-12-04 | 1 | 29 | Uploaded data (2.6G)* |
| ST002435 | Metabolomics analysis of plasma from CHCHD10S59L/+ KI mice | Mus musculus | INSERM | MS | 2023-12-04 | 1 | 28 | Uploaded data (1.6G)* |
