PXD016718-1

PXD016718 is an original dataset announced via ProteomeXchange.

Title	BRAWNIN: A sORF-encoded Peptide Essential for Vertebrate Mitochondrial Complex III
Description	The emergence of small open reading frame (sORF)-encoded peptides (SEPs) is rapidly expanding the known proteome at the lower end of the size distribution. Here, we show that the mitochondrial proteome is enriched for proteins smaller than 100 a.a. (defined as SEPs). Using a prediction and validation pipeline for small open-reading-frame (sORF)-encoded peptides (SEPs), we report the discovery of 16 endogenous nuclear encoded, mitochondrial-localized SEPs (mito-SEPs). Through functional prediction, proteomics, metabolomics and metabolic flux modeling, we demonstrate that BRAWNIN (BR), a 71 amino acid peptide encoded by the C12orf73 gene, is essential for respiratory chain complex III (CIII) assembly. In human cells, BR is induced by the energy-sensing AMPK pathway, and its depletion impairs mitochondrial ATP production. In vivo, BR is enriched in muscle tissues and its maternal zygotic deletion in zebrafish causes complete CIII loss, resulting in severe growth retardation, lactic acidosis and early death. Our findings demonstrate that BR is essential for oxidative phosphorylation across vertebrate species. We propose that mito-SEPs are an untapped resource for essential regulators of oxidative metabolism. The dataset included in this entry is for the Zebrafish and MEF BR knockouts.
HostingRepository	PRIDE
AnnounceDate	2020-03-18
AnnouncementXML	Submission_2020-03-18_05:05:48.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Stroud
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Danio rerio (Zebrafish) (Brachydanio rerio); NCBI TaxID: 7955;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-12 03:41:30	ID requested
⏵ 1	2020-03-18 05:05:50	announced

Zhang S, Relji, ć B, Liang C, Kerouanton B, Francisco JC, Peh JH, Mary C, Jagannathan NS, Olexiouk V, Tang C, Fidelito G, Nama S, Cheng RK, Wee CL, Wang LC, Duek Roggli P, Sampath P, Lane L, Petretto E, Sobota RM, Jesuthasan S, Tucker-Kellogg L, Reversade B, Menschaert G, Sun L, Stroud DA, Ho L, Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly. Nat Commun, 11(1):1312(2020) [pubmed]

submitter keyword: sORF, mitochondria, OXPHOS, uORF, zebrafish

David Stroud
contact affiliation	Department of Biochemistry and Molecular Biology Bio21 Molecular Science and Biotechnology Institute Third floor, room 368 The University of Melbourne Victoria 3010 Australia
contact email	david.stroud@unimelb.edu.au
lab head
David Stroud
contact affiliation	The University of Melbourne
contact email	david.stroud@unimelb.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD016718
     1. Label: PRIDE project
     2. Name: BRAWNIN: A sORF-encoded Peptide Essential for Vertebrate Mitochondrial Complex III