PXD029410-1

PXD029410 is an original dataset announced via ProteomeXchange.

Title	Parkinson's disease protein PARK7 prevents metabolite and protein damage caused by a glycolytic metabolite
Description	Early-onset Parkinson's disease can be caused by mutations in the gene PARK7. Many functions have been proposed for PARK7, but in vivo evidence is largely lacking or conflicting with enzymological data. Here, we provide unequivocal evidence that PARK7 and its orthologues can prevent damage of proteins and metabolites inflicted by the glycolytic intermediate 1,3-bisphosphoglycerate, without changing the abundance of this metabolite. In the absence of PARK7, several glycerate-modified metabolites, as well as numerous glycerate- or phosphoglycerate-modified proteins accumulate in human cell lines, mouse brain and flies. This gives an explanation for the pleiotropic effects of PARK7, indicates that spontaneous metabolic damage contributes to the development of hereditary Parkinson's disease, and opens new roads for future therapeutic approaches. Submitted here are the proteomics analyses, where we identify and quantify glyceroyl- and phosphoglyceroyl-modifications of lysine residues in 5 different experimental models. 1. The human colorectal cancer cell line HCT116 was analyzed in four different conditions: a. Wild type cells transduced with an empty recombinant empty lentivirus b. PARK7 knockout cells transduced with an empty recombinant empty lentivirus c. PARK7 knockout cells transduced with a recombinant lentivirus driving expression of PARK7. 2. Brain samples from wild type and PARK7 knockout mice. 3. Red blood cell lysates from wild type and PARK7 knockout mice 4. Whole body extracts from wild type and DJ1beta knockout Drosophila melanogaster 5. In vitro reactions where 1,3-bisphosphoglycerate was produced either by GAPDH or PGK, in the presence and absence of PARK7. Samples were a. Enzymes in the absence of any cofactors (i.e. no 1,3-BPG production) b. Production via GAPDH (using glyceraldehyde 3-phosphate, phosphate and NAD+ as substrates) in the presence or absence of PARK7 c. Production via PGK (using 3-phosphoglycerate and ATP as substrates) in the presence or absence of PARK7.
HostingRepository	PRIDE
AnnounceDate	2022-01-26
AnnouncementXML	Submission_2022-01-26_07:25:32.049.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Isaac Heremans
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Oryctolagus cuniculus; NCBI TaxID: 9986; scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932; scientific name: Drosophila melanogaster (Fruit fly); NCBI TaxID: 7227;
ModificationList	N6-(3-phosphoglyceryl)-L-lysine; phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-28 08:53:10	ID requested
⏵ 1	2022-01-26 07:25:32	announced
2	2022-01-26 11:39:57	announced	2022-01-26: Updated publication reference for PubMed record(s): 35046029.

Dataset with its publication pending

submitter keyword: glycolysis, PARK7, DJ1, Parkinson's disease, posttranslational modification, glycerate, phosphoglycerate, glyceroyl, phosphoglyceroyl

Guido Thomas Bommer
contact affiliation	Groupe de recherche Metabolique (GRM), BCHM, Institut de Duve, Université Catholique de Louvain, Belgium
contact email	guido.bommer@uclouvain.be
lab head
Isaac Heremans
contact affiliation	Université Catholique de Louvain Institut de Duve
contact email	isaac.heremans@uclouvain.be
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029410
     1. Label: PRIDE project
     2. Name: Parkinson's disease protein PARK7 prevents metabolite and protein damage caused by a glycolytic metabolite