Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in Drosophila
- Harvard University, United States
- Howard Hughes Medical Institute, Yale University, United States
- Baylor College of Medicine, United States
- Lawrence Berkeley National Laboratory, United States
Abstract
Naturally produced peptides (<100 amino acids) are important regulators of physiology, development, and metabolism. Recent studies have predicted that thousands of peptides may be translated from transcripts containing small open reading frames (smORFs). Here, we describe two peptides in Drosophila encoded by conserved smORFs, Sloth1 and Sloth2. These peptides are translated from the same bicistronic transcript and share sequence similarities, suggesting that they encode paralogs. Yet, Sloth1 and Sloth2 are not functionally redundant, and loss of either peptide causes animal lethality, reduced neuronal function, impaired mitochondrial function, and neurodegeneration. We provide evidence that Sloth1/2 are highly expressed in neurons, imported to mitochondria, and regulate mitochondrial complex III assembly. These results suggest that phenotypic analysis of smORF genes in Drosophila can provide a wealth of information on the biological functions of this poorly characterized class of genes.
Data availability
The current manuscript did not generate any datasets. Raw gel and western image source files are present in Supplemental File 4, which can be downloaded at:https://doi.org/10.5061/dryad.83bk3j9vc
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Data from: Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in DrosophilaDryad Digital Repository, doi:10.5061/dryad.83bk3j9vc.
Article and author information
Author details
Funding
Damon Runyon Foundation
- Justin A Bosch
National Institutes of Health (R01GM084947)
- Susan Celniker
National Institutes of Health (R01GM067761)
- Susan Celniker
National Institutes of Health (R24OD019847)
- Susan Celniker
National Institutes of Health (NHGRI HG009352)
- Susan Celniker
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in Drosophila
eLife 11:e82709.
https://doi.org/10.7554/eLife.82709
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