PXD044812-1

PXD044812 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-23 14:05:51	ID requested
⏵ 1	2023-08-23 14:13:49	announced

Dataset with its publication pending

submitter keyword: IP-MassSpec,K562, PREPL, NME6

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

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

• PRIDE
  1. PXD044812
     1. Label: PRIDE project
     2. Name: Regulators of mitonuclear balance link mitochondrial metabolism to mtDNA expression