Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in Drosophila

Bosch, Justin A.; Ugur, Berrak; Pichardo‐Casas, Israel; Rabasco, Jordan; Escobedo, Felipe; Zuo, Zhuang; Brown, Ben; Celniker, S; Sinclair, David; Bellen, Hugo J.; Perrimon, Norbert

doi:10.7554/elife.82709

Cited by 8 publications

(3 citation statements)

References 86 publications

(117 reference statements)

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“…Interestingly, 40% of smORF peptides display a motif, that could be useful to address its biological function. More than 10% of smORF peptides appear to be addressed to mitochondria, suggesting a tendency of the smORF peptides to localise to this organelle compared to the whole proteome (6%) as previously observed (Bosch et al, 2022; van Heesch et al, 2019). Furthermore, the phenotypes obtained are diverse, affecting cell survival, segment fusion or tissue growth, suggesting that smORF peptides are involved in all cellular processes.…”

Section: Discussionsupporting

confidence: 70%

The pleiotropic functions of Pri smORF peptides synchronise leg development regulators

Markus

Pelletier

Boube

et al. 2023

Preprint

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The last decade witnesses the emergence of the abundant family of smORF peptides, encoded by small ORF (<100 codons), whose biological functions remain largely unexplored. Bioinformatic analyses here identify hundreds of putative smORF peptides expressed in Drosophila imaginal leg discs. Thanks to a functional screen in legs, we found smORF peptides involved in morphogenesis, including the pioneer smORF peptides Pri. Since we identified its target Ubr3 in the epidermis and pri was known to control leg development through misunderstood mechanisms, we investigated the role of Ubr3 in mediating pri function in legs. We found that pri play several roles during leg development both in patterning and in cell survival. At larval pupal transition, Pri peptides cooperate with Ubr3 to insure cell survival and leg morphogenesis. Earlier, during larval stage, pri activates independently of Ubr3 tarsal transcriptional programs and Notch and EGFR signalling pathways. Our results highlight Ubr3 dependent and independent functions of Pri peptides and their pleiotropy. Moreover, we reveal that the smORF peptide family is a reservoir of overlooked developmental regulators, displaying distinct molecular functions and orchestrating leg development.

show abstract

Section: Discussionsupporting

confidence: 70%

The pleiotropic functions of Pri smORF peptides synchronise leg development regulators

Markus

Pelletier

Boube

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Interestingly, 40% of smORF peptides display a motif, that could be useful to address its biological function. More than 10% of smORF peptides appear to be addressed to mitochondria, suggesting a tendency of the smORF peptides to localize to this organelle compared to the whole proteome (6%) as previously observed [43,44]. Furthermore, the phenotypes obtained are diverse, affecting cell survival, segment fusion or tissue growth, suggesting that smORF peptides are involved in all cellular processes.…”

Section: Smorf Peptides Provide a Pool Of Novel Developmental Actorssupporting

confidence: 55%

The pleiotropic functions of Pri smORF peptides synchronize leg development regulators

Markus,

Pelletier,

Boube

et al. 2023

PLoS Genet

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The last decade witnesses the emergence of the abundant family of smORF peptides, encoded by small ORF (<100 codons), whose biological functions remain largely unexplored. Bioinformatic analyses here identify hundreds of putative smORF peptides expressed in Drosophila imaginal leg discs. Thanks to a functional screen in leg, we found smORF peptides involved in morphogenesis, including the pioneer smORF peptides Pri. Since we identified its target Ubr3 in the epidermis and pri was known to control leg development through poorly understood mechanisms, we investigated the role of Ubr3 in mediating pri function in leg. We found that pri plays several roles during leg development both in patterning and in cell survival. During larval stage, pri activates independently of Ubr3 tarsal transcriptional programs and Notch and EGFR signaling pathways, whereas at larval pupal transition, Pri peptides cooperate with Ubr3 to insure cell survival and leg morphogenesis. Our results highlight Ubr3 dependent and independent functions of Pri peptides and their pleiotropy. Moreover, we reveal that the smORF peptide family is a reservoir of overlooked developmental regulators, displaying distinct molecular functions and orchestrating leg development.

show abstract

“…These studies and others have identified smaller proteins (often defined as less than 100 amino acids) called micropeptides or small Open Reading Frames (smORFs), that localize inside mitochondria (Tharakan and Sawa, 2021;Zheng and Xiang, 2022). In metazoans, these internal mitochondrial micropeptides have been frequently implicated in critical functions such as the assembly of respiratory complexes (Bosch et al, 2022;Chu et al, 2019;Rathore et al, 2018;Zhang et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

An intermembrane space protein facilitates completion of mitochondrial division in yeast

Connor

Matta

Friedman

2023

Preprint

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Mitochondria are highly dynamic double membrane-bound organelles that maintain their shape in part through fission and fusion. Mitochondrial fission is performed by the dynamin-related protein Dnm1 (Drp1 in humans), a large GTPase that constricts and divides the mitochondria in a GTP hydrolysis-dependent manner. However, it is unclear whether factors inside mitochondria help coordinate the process and if Dnm1/Drp1 activity alone is sufficient to complete fission of both mitochondrial membranes. Here, we identify an intermembrane space protein required for mitochondrial fission in yeast, which we propose to name Mdi1. Loss of Mdi1 leads to hyper-fused mitochondria networks due to defects in mitochondrial fission, but not lack of Dnm1 recruitment to mitochondria. Mdi1 plays a conserved role in fungal species and its homologs contain a putative amphipathic alpha-helix, mutations in which disrupt mitochondrial morphology. One model to explain these findings is that Mdi1 associates with and distorts the mitochondrial inner membrane to enable Dnm1 to robustly complete fission. Our work reveals that Dnm1 cannot efficiently divide mitochondria without the coordinated function of a protein that resides inside mitochondria.

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Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in Drosophila

Cited by 8 publications

References 86 publications

The pleiotropic functions of Pri smORF peptides synchronise leg development regulators

The pleiotropic functions of Pri smORF peptides synchronise leg development regulators

The pleiotropic functions of Pri smORF peptides synchronize leg development regulators

An intermembrane space protein facilitates completion of mitochondrial division in yeast

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