PXD021015

PXD021015 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-19 23:38:07	ID requested
⏵ 1	2022-11-29 02:35:57	announced

Dataset with its publication pending

submitter keyword: LFQ, initiation,mitochondrial, translation

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

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PRIDE project URI

• PRIDE
  1. PXD021015
     1. Label: PRIDE project
     2. Name: Distinct roles for human mtIF2 and mtIF3 in non-canonical mitochondrial translation