PXD019690

PXD019690 is an original dataset announced via ProteomeXchange.

Title	Neuronal metabolic rewiring promotesresilience to neurodegeneration caused by mitochondrial dysfunction
Description	Neurodegeneration in mitochondrial disorders is considered irreversible because of limited metabolic plasticity in neurons, yet the cell-autonomous implications of mitochondrial dysfunction for neuronal metabolism in vivo are poorly understood. Here, we profiled the cell-specific proteome of Purkinje neurons undergoing progressive OXPHOS deficiency caused by disrupted mitochondria fusion dynamics. We found that mitochondrial dysfunction triggers a profound rewiring of the proteomic landscape culminating in the sequential activation of precise metabolic programs preceding cell death. Surprisingly, we identified a marked induction of pyruvate carboxylase (PCx) and other key anaplerotic enzymes involved in replenishing intermediates into the TCA cycle. Suppression of PCx aggravated neurodegeneration, showing that anaplerosis is protective in OXPHOS-deficient neurons. Restoration of mitochondrial fusion in end-stage degenerating neurons fully reversed these metabolic hallmarks thereby preventing cell death. Our findings identify a previously unappreciated pathway conferring resilience to mitochondrial dysfunction and show that neurodegeneration can be reversed even at advanced disease stages.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:51:11.083.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ilian Atanassov
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-10 03:44:50	ID requested
1	2020-08-02 22:51:13	announced
2	2020-11-22 23:00:37	announced	2020-11-23: Updated publication reference for PubMed record(s): 32923630.
3	2020-11-23 07:03:45	announced	2020-11-23: Updated publication reference for PubMed record(s): 32923630. 2020-11-23: Updated publication reference for PubMed record(s): 32923630.
⏵ 4	2023-11-14 08:51:11	announced	2023-11-14: Updated project metadata.

Motori E, Atanassov I, Kochan SMV, Folz-Donahue K, Sakthivelu V, Giavalisco P, Toni N, Puyal J, Larsson NG, Neuronal metabolic rewiring promotes resilience to neurodegeneration caused by mitochondrial dysfunction. Sci Adv, 6(35):eaba8271(2020) [pubmed]

submitter keyword: Anaplerosis, labe-free, TMT,Purkinje neurons, mitofusin 2

Nils-Göran Larsson
contact affiliation	Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Karolinska Institutet, Stockholm, Sweden.
contact email	Nils-Goran.Larsson@ki.se
lab head
Ilian Atanassov
contact affiliation	Max Planck Institute for Biology of Aging
contact email	Ilian.Atanassov@age.mpg.de
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/2020/08/PXD019690

PRIDE project URI

• PRIDE
  1. PXD019690
     1. Label: PRIDE project
     2. Name: Neuronal metabolic rewiring promotesresilience to neurodegeneration caused by mitochondrial dysfunction