PXD017683 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Skeletal Muscle from Mice fed with HFD LC-MSMS |
Description | Whether muscle mitochondrial dysfunction is the cause or consequence of metabolic disorders remains controversial. Herein, we demonstrate that inhibition of mitochondrial ATP synthase in muscle in vivo alters whole-body lipid homeostasis. Mice with restrained activity of the enzyme presented intrafiber lipid droplets, dysregulation of acyl-glycerides and higher visceral adipose tissue deposits, causing these animals to be prone to insulin resistance. This mitochondrial energy crisis increase lactate production, prevents fatty acid β-oxidation, and forces the catabolism of branched-chain amino acids (BCAA) to provide acetyl-CoA for de novo lipid synthesis. In turn, muscle acetyl-CoA accumulation feeds back to oxidative phosphorylation dysfunction through the acetylation-dependent inhibition of respiratory complex II that results in augmented ROS production. Finally, by screening 702 FDA-approved drugs, we identified edaravone as a potent mitochondrial antioxidant and enhancer. The edaravone-driven restoration of ROS and lipid homeostasis in skeletal muscle reestablished insulin sensitivity, thus suggesting that muscular mitochondrial perturbations are a direct cause in the setting of metabolic disorders and repurposing edaravone as a potential treatment for these diseases. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-08 |
AnnouncementXML | Submission_2024-10-08_12:51:12.723.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD017683 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Cristina Sánchez González |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | HNE; GG; PropylNAGthiazoline; Bacillosamine; GluGlu; Hex; Methylphosphonate; Bromobimane; Delta:H(4)C(2)O(-1)S(1); Decanoyl; Propionamide; GlycerylPE; BADGE; Dipyrrolylmethanemethyl; Deamidated; sulfo+amino; Hydroxyfarnesyl; Trp->Oxolactone; Methylamine; DHP; azole; Myristoyl; Cation:K; iTRAQ4plex-116 reporter+balance reagent acylated residue; Delta:S(-1)Se(1); Octanoyl; Gln->pyro-Glu; Met->Hsl; Diethylphosphate; Guanidinyl; Menadione-HQ; DAET; Dehydro; NA-LNO2; Chlorination; Fluoro; Ammonia-loss; Ethylphosphate; Oxidation; Diphthamide; AEC-MAEC; Ethanedithiol; Carboxy; Met->Hpg; NO_SMX_SIMD; 4-ONE; PET; Quinone; Ethanolamine; Cation:Na; Nitrosyl; Palmitoleyl; Trp->Hydroxykynurenin; Sulfo; Deoxy; BEMAD_ST; Malonyl; Methyl+Deamidated; HPG; Formyl; Carbamyl; Arg->Orn; BEMAD_C; 3-deoxyglucosone; Thiophospho; Sulfide; PhosphoUridine; Met->Aha; Amino; Ammonium; Dimethyl; 2-succinyl; Menadione; NA-OA-NO2; Delta:H(5)C(2); Cation:Cu[I]; Pro->Pyrrolidone; Crotonaldehyde; Met->Hse; Dethiomethyl; Amidated; Cys->Dha; Pro->pyro-Glu; Ethanolyl; EGCG2; Phospho; Propargylamine; Acetyl; Nmethylmaleimide+water; Cation:Ni[II]; Nitro; ADP-Ribosyl; Methylthio; Carboxymethyl; 4-ONE+Delta:H(-2)O(-1); HexNAc; Phosphoadenosine; Carbamidomethyl; Cation:Ca[II]; Biotin-PEO-Amine; HNE+Delta:H(2); Trioxidation; trifluoro; Puromycin; Glu->pyro-Glu; GluGluGluGlu; Arg->Npo; Carboxyethyl; Biotin-HPDP; MercaptoEthanol; Hydroxymethyl; EDT-maleimide-PEO-biotin; Delta:H(2)C(2); Ethyl; Cation:Li; iTRAQ4plex; O-Isopropylmethylphosphonate; Cation:Fe[II]; phosphoRibosyl; Cyano; Isopropylphospho; FTC; Methyl; AEBS; Methylmalonylation; Phosphopropargyl; Pyridylethyl; Delta:H(4)C(3); Didehydro; Cytopiloyne+water; Trp->Kynurenin; DimethylArsino; Glu; Pro->Pyrrolidinone; Arg->GluSA; Iodo; Arg2PG; Delta:Se(1); Diisopropylphosphate; Cys->Oxoalanine; Hydroxycinnamyl; Nmethylmaleimide; G-H1; ethylamino; maleimide; O-Methylphosphate; HCysteinyl; Dehydrated; Biotin; Dioxidation; Ethyl+Deamidated; Amidino; Carbofuran |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-02-21 07:27:49 | ID requested | |
⏵ 1 | 2024-10-08 12:51:13 | announced | |
Publication List
10.15252/embj.2019103812; |
10.6019/PXD017683; |
S, á, nchez-Gonz, á, lez C, Nuevo-Tapioles C, Herrero Mart, í, n JC, Pereira MP, Serrano Sanz S, Ram, í, rez de Molina A, Cuezva JM, Formentini L, Dysfunctional oxidative phosphorylation shunts branched-chain amino acid catabolism onto lipogenesis in skeletal muscle. EMBO J, 39(14):e103812(2020) [pubmed] |
Keyword List
submitter keyword: Mouse Skeletal Muscle HFD |
Contact List
Laura Formentini |
contact affiliation | PI in de Department of Molecular Biology in Centro de Biología Molecular ‘“Severo Ochoa’” (CBMSO)- Universidad Autónoma de Madrid (UAM), leading the project "Role of mitochondrial bioenergetics in skeletal muscle secretrome during exercise and pathology". |
contact email | lformentini@cbm.csic.es |
lab head | |
Cristina Sánchez González |
contact affiliation | Centro de Biología Molecular Severo Ochoa - Universidad Autónoma de Madrid (CBMSO-UAM) |
contact email | cristina.sanchez@cbm.csic.es |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD017683
- Label: PRIDE project
- Name: Skeletal Muscle from Mice fed with HFD LC-MSMS