PXD045443

PXD045443 is an original dataset announced via ProteomeXchange.

Title	METTL17 is an Fe-S cluster checkpoint for mitochondrial translation
Description	Friedreich’s ataxia (FA) is the most common monogenic mitochondrial disease. FA is caused by a depletion of the mitochondrial protein frataxin (FXN), an iron-sulfur (Fe-S) cluster biogenesis factor. To better understand the cellular consequences of FA, we performed quantitative proteome profiling of human cells depleted for FXN. Nearly every known Fe-S cluster-containing protein was depleted in the absence of FXN, indicating that as a rule, cluster binding confers stability to Fe-S proteins. Proteomic and genetic interaction mapping identified impaired mitochondrial translation downstream of FXN loss, and specifically highlighted the methyltransferase-like protein METTL17 as a candidate effector. Using comparative sequence analysis, mutagenesis, biochemistry and cryogenic electron microscopy we show that METTL17 binds to the mitoribosomal small subunit during late assembly and harbors a previously unrecognized [Fe4S4]2+ cluster required for its stability on the mitoribosome. Notably, METTL17 overexpression rescued the mitochondrial translation and bioenergetic defects, but not the cellular growth, of FXN depleted cells. Our data suggest that METTL17 serves as an Fe-S cluster checkpoint: promoting the translation and assembly of Fe-S cluster rich OXPHOS proteins only when Fe-S cluster levels are replete.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:18:43.731.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tslil Ast
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-18 03:55:23	ID requested
1	2023-12-27 10:52:54	announced
⏵ 2	2024-10-22 06:18:44	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: METTL17, Friedreich’s ataxia,FXN, Fe-S clusters

Vamsi K. Mootha
contact affiliation	1.Department of Molecular Biology and Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA, 2.Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA, 3.Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
contact email	vamsi_mootha@hms.harvard.edu
lab head
Tslil Ast
contact affiliation	The Weizmann Institute of Science
contact email	tslil.ast@weizmann.ac.il
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/2023/12/PXD045443

PRIDE project URI

• PRIDE
  1. PXD045443
     1. Label: PRIDE project
     2. Name: METTL17 is an Fe-S cluster checkpoint for mitochondrial translation