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

Area of Science:

• Molecular Biology
• Genetics
• Neuroscience

Background:

• Naturally produced peptides (<100 amino acids) regulate key physiological processes.
• Thousands of peptides may originate from small open-reading frames (smORFs).
• The biological functions of smORF-encoded peptides remain largely uncharacterized.

Purpose of the Study:

• To characterize two novel peptides, Sloth1 and Sloth2, encoded by conserved smORFs in Drosophila.
• To investigate the function and biological roles of Sloth1 and Sloth2.
• To explore the significance of smORF-derived peptides in biological systems.

Main Methods:

• Identification and characterization of peptides encoded by conserved smORFs in Drosophila.
• Analysis of Sloth1 and Sloth2 expression patterns and localization.
• Functional studies involving loss-of-function mutations to assess phenotypic consequences.
• Investigation of mitochondrial function and complex III assembly.

Main Results:

• Two peptides, Sloth1 and Sloth2, are translated from the same bicistronic transcript and are highly expressed in neurons.
• Loss of Sloth1 or Sloth2 results in animal lethality, impaired neuronal and mitochondrial function, and neurodegeneration.
• Sloth1/2 peptides are imported into mitochondria and regulate mitochondrial complex III assembly.

Conclusions:

• Sloth1 and Sloth2, encoded by smORFs, are essential for Drosophila viability and function.
• These peptides play critical roles in neuronal health and mitochondrial complex III assembly.
• Phenotypic analysis of smORF genes in Drosophila offers valuable insights into the functions of this gene class.