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Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly

Zhang, Shan
Reljić, Boris
Liang, Chao
Kerouanton, Baptiste
Francisco, Joel Celio
Peh, Jih Hou
Jagannathan, Narendra Suhas
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Published in Nature communications. 2020, vol. 11, no. 1, 1312
Abstract 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, particularly the respiratory chain, is enriched for small proteins. Using a prediction and validation pipeline for 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, a 71 a.a. peptide encoded by C12orf73, is essential for respiratory chain complex III (CIII) assembly. In human cells, BRAWNIN is induced by the energy-sensing AMPK pathway, and its depletion impairs mitochondrial ATP production. In zebrafish, Brawnin deletion causes complete CIII loss, resulting in severe growth retardation, lactic acidosis and early death. Our findings demonstrate that BRAWNIN is essential for vertebrate oxidative phosphorylation. We propose that mito-SEPs are an untapped resource for essential regulators of oxidative metabolism.
Keywords AcidosisLactic/geneticsAnimalsAnimalsGenetically ModifiedDisease ModelsAnimalElectron Transport Complex III/metabolismFemaleGene Knockdown TechniquesGrowth Disorders/geneticsHumansMaleMetabolomicsMitochondria/metabolismMitochondrial Proteins/genetics/metabolismModelsAnimalModelsBiologicalOpen Reading Frames/geneticsOxidative PhosphorylationPeptides/genetics/metabolismProteomicsZebrafish/genetics/growth & developmentZebrafish Proteins/genetics/metabolism
PMID: 32161263
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Research group Calipho (80)
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ZHANG, Shan et al. Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly. In: Nature Communications, 2020, vol. 11, n° 1, p. 1312. doi: 10.1038/s41467-020-14999-2 https://archive-ouverte.unige.ch/unige:142219

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Deposited on : 2020-09-29

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