التفاصيل البيبلوغرافية
| العنوان: |
BRAWNIN: A sORF-encoded Peptide Essential for Vertebrate Mitochondrial Complex III Assembly |
| المؤلفون: |
Lei Sun, Loo Chien Wang, Lydie Lane, Lena Ho, Enrico Petretto, David A. Stroud, Francisco J, Prabha Sampath, Carol Tang, Baptiste Kerouanton, Suresh Jesuthasan, Narendra Suhas Jagannathan, Srikanth Nama, Bruno Reversade, Olexiouk, Caroline Lei Wee, Siyuan Zhang, Duek Roggli P, Radoslaw M. Sobota, Fidelito G, Chao Liang, Hou Peh J, Cheng R, Gerben Menschaert, Mary C, Lisa Tucker-Kellogg |
| بيانات النشر: |
Cold Spring Harbor Laboratory, 2020. |
| سنة النشر: |
2020 |
| مصطلحات موضوعية: |
0303 health sciences, biology, Chemistry, Oxidative phosphorylation, Mitochondrion, biology.organism_classification, Proteomics, medicine.disease, Cell biology, 03 medical and health sciences, Open reading frame, 0302 clinical medicine, Lactic acidosis, Proteome, medicine, Flux (metabolism), Zebrafish, 030217 neurology & neurosurgery, 030304 developmental biology |
| الوصف: |
The emergence of small open reading frame (sORF)-encoded peptides (SEPs) is rapidly expanding the known proteome at the lower end of the size distribution1,2. Here, we show that the mitochondria proteome is enriched for proteins smaller than 100 a.a. (defined as SEPs). Using a mitochondrial prediction and validation pipeline for small open-reading-frame (sORF)-encoded peptides (SEPs), we report the discovery of 16 endogenous mitochondrial SEPs (mito-SEPs) associated with oxidative phosphorylation (OXPHOS). Through functional prediction, proteomics, metabolomics and metabolic flux modeling, we demonstrate that BRAWNIN (BR), a 71 amino acid peptide encoded by theC12orf73gene, 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. |
| اللغة: |
English |
| DOI: |
10.1101/2020.01.31.926402 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9e0f5537b2255ec28765e1c0daccd50f |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....9e0f5537b2255ec28765e1c0daccd50f |
| قاعدة البيانات: |
OpenAIRE |