PXD032363-2

PXD032363 is an original dataset announced via ProteomeXchange.

Title	Mitoproteomics of neuronal mitochondria of EAE mice
Description	Inflammation in the central nervous system (CNS) can impair the function of neuronal mitochondria and contributes to axon degeneration in the common neuroinflammatory disease multiple sclerosis (MS). Here we combine cell type-specific mitochondrial proteomics with in vivo biosensor imaging to dissect how inflammation alters the molecular composition and functional capacity of neuronal mitochondria. Neuroinflammatory lesions in the mouse spinal cord cause widespread and persisting axonal ATP depletion, which precedes mitochondrial oxidation and calcium overload. This early axonal energy crisis is associated with impaired electron transport chain function, but also an upstream dysbalance of tricarboxylic acid (TCA) cycle enzymes. Isocitrate dehydrogenase 3 (Idh3), the rate limiting enzyme of the TCA cycle, is depleted in neuronal mitochondria in experimental models and in human MS lesions. Notably, viral overexpression of Idh3 can rectify the axonal energy deficits, suggesting that TCA cycle dysfunction in neuroinflammation may be amendable to therapy.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:06:04.622.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stephan Mueller
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-17 04:33:43	ID requested
1	2023-10-18 08:19:25	announced
⏵ 2	2023-11-14 09:06:10	announced	2023-11-14: Updated project metadata.
3	2024-10-22 06:06:16	announced	2024-10-22: Updated project metadata.

Tai YH, Engels D, Locatelli G, Emmanouilidis I, Fecher C, Theodorou D, M, ü, ller SA, Licht-Mayer S, Kreutzfeldt M, Wagner I, de Mello NP, Gkotzamani SN, Trov, ò L, Kendirli A, Aljovi, ć A, Breckwoldt MO, Naumann R, Bareyre FM, Perocchi F, Mahad D, Merkler D, Lichtenthaler SF, Kerschensteiner M, Misgeld T, Targeting the TCA cycle can ameliorate widespread axonal energy deficiency in neuroinflammatory lesions. Nat Metab, 5(8):1364-1381(2023) [pubmed]

submitter keyword: Mitochondria, IDH3, Neurons

Stefan F. Lichtenthaler
contact affiliation	DZNE Munich Neuroproteomics Feodor-Lynen Str. 17 81377 Munich Germany
contact email	stefan.lichtenthaler@dzne.de
lab head
Stephan Mueller
contact affiliation	DZNE Munich Neuroproteomics
contact email	stephan.mueller@dzne.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD032363
     1. Label: PRIDE project
     2. Name: Mitoproteomics of neuronal mitochondria of EAE mice