PXD021015 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Distinct roles for human mtIF2 and mtIF3 in non-canonical mitochondrial translation |
Description | The production of mitochondrial OXPHOS complexes is central to cellular metabolism, although the molecular details of mitochondrial translation remain enigmatic. It is widely held that translation initiation in human mitochondria proceeds similarly to bacterial systems, with mRNA binding the mitoribosomal small subunit in the presence of initiation factors, mtIF2and mtIF3, and initiator tRNA. However, unlike in bacteria, most human mitochondrial mRNAs do not possess 5′ leader sequences that mediate binding to the small subunit. Thus, how leaderless mRNAs are recognized by the mitoribosome is not known. By developing a single-molecule, fluorescence-based in vitro translation initiation assay, alongside the biochemical and genetic characterization of cellular knockouts of mitochondrial translation factors, we describe a mechanism for non-canonical translation initiation in human mitochondria. We show leaderless mt-mRNAs can be loaded onto 55S monosomes and translated independently of mtIF3 activity. However, in the case of the bicistronic ATP8/ATP6 transcript, translation of the downstream open reading frame (ORF) is dependent upon mtIF3 and is uncoupled from the upstream leaderless ORF, highlighting distinct role for the human initiation factor. Furthermore, we found mtIF2 to be essential for mitochondrial protein synthesis, but not monosome formation, while mitoribosome recycling was important for mitoribosome homeostasis. These data define an important evolutionary diversion of mitochondrial translation system, and further our fundamental understanding of a process central to eukaryotic metabolism. |
HostingRepository | PRIDE |
AnnounceDate | 2022-11-29 |
AnnouncementXML | Submission_2022-11-29_02:35:56.963.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Ilian Atanassov |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-08-19 23:38:07 | ID requested | |
⏵ 1 | 2022-11-29 02:35:57 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: LFQ, initiation,mitochondrial, translation |
Contact List
JoannaRorbach |
contact affiliation | Department of Medical Biochemistry and Biophysics, Division of Molecular Metabolism, Karolinska Institutet, Biomedicum, 171 65 Solna, Sweden Max Planck Institute Biology of Ageing - Karolinska Institutet Laboratory, Karolinska Institutet, Stockholm, Sweden |
contact email | Joanna.rorbach@ki.se |
lab head | |
Ilian Atanassov |
contact affiliation | Max Planck Institute for Biology of Aging |
contact email | Ilian.Atanassov@age.mpg.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD021015
- Label: PRIDE project
- Name: Distinct roles for human mtIF2 and mtIF3 in non-canonical mitochondrial translation