PXD044812 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Regulators of mitonuclear balance link mitochondrial metabolism to mtDNA expression |
Description | Mitochondrial 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. |
HostingRepository | PRIDE |
AnnounceDate | 2023-08-23 |
AnnouncementXML | Submission_2023-08-23_14:13:48.719.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | NicholasKramer |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | LTQ Orbitrap |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-08-23 14:05:51 | ID requested | |
⏵ 1 | 2023-08-23 14:13:49 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: IP-MassSpec,K562, PREPL, NME6 |
Contact List
StirlingChurchman |
contact affiliation | Department of Genetics, Harvard Medical School |
contact email | churchman@genetics.med.harvard.edu |
lab head | |
NicholasKramer |
contact affiliation | Harvard Medical School |
contact email | nicholas_kramer@hms.harvard.edu |
dataset submitter | |
Full Dataset Link List
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/2023/08/PXD044812 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD044812
- Label: PRIDE project
- Name: Regulators of mitonuclear balance link mitochondrial metabolism to mtDNA expression