PXD027754

PXD027754 is an original dataset announced via ProteomeXchange.

Title	Metabolic reprogramming during hyperammonemia targets mitochondrial function and post-mitotic senescence
Description	Ammonia is a cytotoxic metabolite with pleotropic molecular and metabolic effects in non-hepatic tissue/cells targeting mitochondrial oxidative function that may contribute to post-mitotic senescence. Global molecular responses were determined by analysis of unbiased data followed by experimental validation of critical functional consequences in hyperammonemic differentiated myotubes and skeletal muscle from the portacaval anastomosis (PCA) rat. Integrating whole cell transcriptome with whole cell and mitochondrial proteome from hyperammonemic myotubes identified oxidative dysfunction and senescence pathways as being the most enriched with differentially expressed genes/proteins. Hyperammonemia and ammonia-lowering result in distinct clusters of molecular responses. Functional and metabolic studies in hyperammonemic myotubes showed that defects in electron transport chain (ETC) complexes I and III, loss of supercomplex assembly, decreased ATP synthesis, increased free radical generation with oxidative modification of proteins/lipids and increased expression of senescence associated molecular phenotype (SAMP) that were partially reversed by ammonia lowering. Studies in muscle from PCA rats established physiological relevance of our cellular studies. Dysregulated ammonia metabolism causes mitochondrial dysfunction by transcriptional and translational perturbations in multiple pathways with a distinct skeletal muscle SAMP.
HostingRepository	PRIDE
AnnounceDate	2021-11-22
AnnouncementXML	Submission_2021-11-22_06:59:44.696.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD027754
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Ling Li
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-05 10:00:58	ID requested
⏵ 1	2021-11-22 06:59:45	announced

Dataset with its publication pending

submitter keyword: Ammonia, cytotoxic, portacaval anastomosis, PCA, Hyperammonemia

Srinivasan Dasarathy
contact affiliation	Department of Inflammation and Immunity, Gastroenterology and Hepatology. Cleveland Clinic, Cleveland Ohio
contact email	dasaras@ccf.org
lab head
Ling Li
contact affiliation	Cleveland Clinic
contact email	lil5@ccf.org
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/2021/11/PXD027754

PRIDE project URI

• PRIDE
  1. PXD027754
     1. Label: PRIDE project
     2. Name: Metabolic reprogramming during hyperammonemia targets mitochondrial function and post-mitotic senescence