PXD026900-1

PXD026900 is an original dataset announced via ProteomeXchange.

Title	A patient-based Drosophila model for mitochondrial S-Adenosylhomocysteine transport deficiency
Description	The SLC25A26 gene encodes a mitochondrial inner membrane carrier that transports S-adenosylmethionine (SAM) into the mitochondrial matrix in exchange for S-adenosylhomocysteine (SAH). SAM is the predominant methyl-group donor for most cellular methylation processes, of which SAH is produced as a by-product. Pathogenic, bi-allelic SLC25A26 variants are a recognized cause of mitochondrial disease in children, with a severe neonatal-onset caused by decreased SAM transport activity. We describe two, unrelated adult cases presenting with exercise intolerance and mitochondrial myopathy associated with bi-allelic variants in SLC25A26 which lead to marked respiratory chain deficiencies and mitochondrial histopathological abnormalities in skeletal muscle that are comparable to the early-onset cases. We demonstrate using both mouse and fruit fly models that impairment of SAH, rather than SAM, transport across the mitochondrial membrane is the cause of this milder, later onset clinical phenotype. In this submission, the total larval proteome was assessed at two, three and four days after egg laying in mutants expressing a SAMC.R166Q mutation versus wDah genetic background controls. Our finding of a novel pathomechanism associated with a known disease-causing protein highlights the potential of precision medicine in clinical decision making.
HostingRepository	PRIDE
AnnounceDate	2022-01-19
AnnouncementXML	Submission_2022-01-19_13:57:07.213.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Florian Schober
SpeciesList	scientific name: Drosophila melanogaster (Fruit fly); NCBI TaxID: 7227;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-24 03:40:37	ID requested
⏵ 1	2022-01-19 13:57:08	announced

Rosenberger FA, Tang JX, Sergeant K, Moedas MF, Zierz CM, Moore D, Smith C, Lewis D, Guha N, Hopton S, Falkous G, Lam A, Pyle A, Poulton J, Gorman GS, Taylor RW, Freyer C, Wredenberg A, Pathogenic SLC25A26 variants impair SAH transport activity causing mitochondrial disease. Hum Mol Genet, 31(12):2049-2062(2022) [pubmed]

submitter keyword: SAMC, Drosophila, SAM, SAH, methylation, SLC25A26, mitochondria

Anna Wredenberg
contact affiliation	Department of Medical Biochemisty and Biophysics, Karolinska Institute, Sweden
contact email	anna.wredenberg@ki.se
lab head
Florian Schober
contact affiliation	MMK, Karolinska Institute
contact email	florian.schober@ki.se
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/2022/01/PXD026900

PRIDE project URI

• PRIDE
  1. PXD026900
     1. Label: PRIDE project
     2. Name: A patient-based Drosophila model for mitochondrial S-Adenosylhomocysteine transport deficiency