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.
| Study ID | ST002434 |
| Study Title | Metabolomics analysis of heart 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: | SU002523 |
| 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 |
|---|---|---|---|---|
| SA243385 | Heart_16 | CHCHD10S59L/+ | female | Symptomatic |
| SA243386 | Heart_17 | CHCHD10S59L/+ | female | Symptomatic |
| SA243387 | Heart_23 | CHCHD10S59L/+ | female | Symptomatic |
| SA243388 | Heart_22 | CHCHD10S59L/+ | female | Symptomatic |
| SA243377 | Heart_11 | CHCHD10S59L/+ | Male | Symptomatic |
| SA243378 | Heart_9 | CHCHD10S59L/+ | Male | Symptomatic |
| SA243379 | Heart_12 | CHCHD10S59L/+ | Male | Symptomatic |
| SA243380 | Heart_24 | CHCHD10S59L/+ | Male | Symptomatic |
| SA243381 | Heart_18 | CHCHD10S59L/+ | Male | Symptomatic |
| SA243382 | Heart_8 | CHCHD10S59L/+ | Male | Symptomatic |
| SA243383 | Heart_10 | CHCHD10S59L/+ | Male | Symptomatic |
| SA243384 | Heart_7 | CHCHD10S59L/+ | Male | Symptomatic |
| SA243389 | Heart_QC5 | QC | QC | QC |
| SA243390 | Heart_QC4 | QC | QC | QC |
| SA243391 | Heart_QC2 | QC | QC | QC |
| SA243392 | Heart_QC3 | QC | QC | QC |
| SA243393 | Heart_QC1 | QC | QC | QC |
| SA243402 | Heart_13 | Wild-type | female | Symptomatic |
| SA243403 | Heart_19 | Wild-type | female | Symptomatic |
| SA243404 | Heart_14 | Wild-type | female | Symptomatic |
| SA243405 | Heart_20 | Wild-type | female | Symptomatic |
| SA243394 | Heart_21 | Wild-type | Male | Symptomatic |
| SA243395 | Heart_15 | Wild-type | Male | Symptomatic |
| SA243396 | Heart_4 | Wild-type | Male | Symptomatic |
| SA243397 | Heart_6 | Wild-type | Male | Symptomatic |
| SA243398 | Heart_3 | Wild-type | Male | Symptomatic |
| SA243399 | Heart_1 | Wild-type | Male | Symptomatic |
| SA243400 | Heart_2 | Wild-type | Male | Symptomatic |
| SA243401 | Heart_5 | Wild-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℃ |
Combined analysis:
| Analysis ID | AN003964 | AN003965 | AN003966 |
|---|---|---|---|
| Analysis type | MS | MS | MS |
| Chromatography type | HILIC | Reversed phase | Reversed phase |
| Chromatography system | Thermo Dionex Ultimate 3000 | Thermo Dionex Ultimate 3000 | Thermo Dionex Ultimate 3000 |
| Column | Thermo Accucore HILIC (100 x 2.1mm, 2.6um) | Phenomenex Kinetex C18 (150 x 2.1mm, 2.6 um) | Phenomenex Kinetex C18 (150 x 2.1mm, 2.6 um) |
| MS Type | ESI | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap | Orbitrap |
| MS instrument name | Thermo Q Exactive Plus Orbitrap | Thermo Q Exactive Plus Orbitrap | Thermo Q Exactive Plus Orbitrap |
| Ion Mode | POSITIVE | POSITIVE | NEGATIVE |
| Units | relative units | relative units | relative units |
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 |
MS:
| MS ID: | MS003698 |
| Analysis ID: | AN003964 |
| Instrument Name: | Thermo Q Exactive Plus Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | During the full-scan acquisition, which 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: | MS003699 |
| Analysis ID: | AN003965 |
| Instrument Name: | Thermo Q Exactive Plus Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | During the full-scan acquisition, which 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: | MS003700 |
| Analysis ID: | AN003966 |
| Instrument Name: | Thermo Q Exactive Plus Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | During the full-scan acquisition, which 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 |
