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PXD044812-1

PXD044812 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleRegulators of mitonuclear balance link mitochondrial metabolism to mtDNA expression
DescriptionMitochondrial oxidative phosphorylation (OXPHOS) complexes are assembled from proteins encoded by both nuclear and mitochondrial DNA. These dual-origin enzymes pose a complex gene regulatory challenge for cells requiring coordinated gene expression across organelles. To identify genes involved in dual-origin protein complex synthesis, we performed FACS-based genome-wide screens analyzing mutant cells with unbalanced levels of mitochondrial- and nuclear-encoded subunits of Complex IV. We identified novel genes involved in OXPHOS biogenesis, including two uncharacterized genes: PREPL and NME6. We found that PREPL specifically impacts Complex IV biogenesis by acting at the intersection of mitochondrial lipid metabolism and protein synthesis, while NME6, an uncharacterized nucleoside diphosphate kinase (NDPK), controls OXPHOS biogenesis through multiple mechanisms reliant on its NDPK domain. First, NME6 forms a complex with RCC1L, which together perform NDPK activity to maintain local mitochondrial pyrimidine triphosphate levels essential for mitochondrial RNA abundance. Second, NME6 modulates the activity of mitoribosome regulatory complexes, altering mitoribosome assembly and mitochondrial RNA pseudouridylation. Taken together, we propose that NME6 acts as a link between compartmentalized mitochondrial metabolites and mitochondrial gene expression.
HostingRepositoryPRIDE
AnnounceDate2023-08-23
AnnouncementXMLSubmission_2023-08-23_14:13:48.719.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterNicholasKramer
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentLTQ Orbitrap
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-08-23 14:05:51ID requested
12023-08-23 14:13:49announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: IP-MassSpec,K562, PREPL, NME6
Contact List
StirlingChurchman
contact affiliationDepartment of Genetics, Harvard Medical School
contact emailchurchman@genetics.med.harvard.edu
lab head
NicholasKramer
contact affiliationHarvard Medical School
contact emailnicholas_kramer@hms.harvard.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
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