PXD009743

PXD009743 is an original dataset announced via ProteomeXchange.

Title	Mutations in NDUFS1 Cause Metabolic Reprogramming and Disruption of the Electron Transfer
Description	Complex I (CI) is the first enzyme of the mitochondrial respiratory chain and couples the electron transfer with proton pumping. Mutations in genes encoding CI subunits can frequently cause inborn metabolic errors. We applied proteome and metabolome profiling of patient-derived cells harboring pathogenic mutations in two distinct CI genes to elucidate underlying pathomechanisms on the molecular level. Our results indicated that the electron transfer within CI was interrupted in both patients by different mechanisms. We showed that the biallelic mutations in NDUFS1 led to a decreased stability of the entire N-module of CI and disrupted the electron transfer between two iron–sulfur clusters. Strikingly interesting and in contrast to the proteome, metabolome profiling illustrated that the pattern of dysregulated metabolites was almost identical in both patients, such as the inhibitory feedback on the TCA cycle and altered glutathione levels, indicative for reactive oxygen species (ROS) stress. Our findings deciphered pathological mechanisms of CI deficiency to better understand inborn metabolic errors.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:57:58.499.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Meierhofer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2018-05-10 23:50:44	ID requested
1	2019-09-30 03:39:57	announced
2	2019-10-16 04:09:45	announced	2019-10-16: Updated publication reference for PubMed record(s): 31557978.
⏵ 3	2024-10-22 04:58:02	announced	2024-10-22: Updated project metadata.

Ni Y, Hagras MA, Konstantopoulou V, Mayr JA, Stuchebrukhov AA, Meierhofer D, Cause Metabolic Reprogramming and Disruption of the Electron Transfer. Cells, 8(10):(2019) [pubmed]

10.3390/cells8101149;

curator keyword: Biomedical

submitter keyword: proteome profiling, NDUFS1, metabolome profiling, MT-ND5,Mitochondrial complex I

David Meierhofer
contact affiliation	Mass Spectrometry Facility Max Planck Institute for Molecular Genetics Ihnestrasse 63-73 14195 Berlin GERMANY
contact email	meierhof@molgen.mpg.de
lab head
David Meierhofer
contact affiliation	Mass Spectrometry Facility MPIMG
contact email	meierhof@molgen.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/2019/10/PXD009743

PRIDE project URI

• PRIDE
  1. PXD009743
     1. Label: PRIDE project
     2. Name: Mutations in NDUFS1 Cause Metabolic Reprogramming and Disruption of the Electron Transfer