PXD017621

PXD017621 is an original dataset announced via ProteomeXchange.

Title	Mouse Skeletal Muscle mitochondrial bioenergetics 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	2020-07-06
AnnouncementXML	Submission_2020-07-06_07:47:19.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD017621
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	iTRAQ4plex-116 reporter+balance reagent acylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2020-02-19 07:43:15	ID requested
⏵ 1	2020-07-06 07:47:20	announced

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]

submitter keyword: Mouse Skeletal Muscle

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

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017621

PRIDE project URI

• PRIDE
  1. PXD017621
     1. Label: PRIDE project
     2. Name: Mouse Skeletal Muscle mitochondrial bioenergetics LC-MSMS