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Newly-Discovered Small Mitochondrial Protein Essential for Energy Production

Study by researcher by Duke-NUS Medical School and collaborators found a small mitochondrial protein necessary for energy production and its malfunction could be responsible for a range of degenerative diseases.

The report published in the journal Nature Communications demonstrated that zebrafish lacking the small protein, which the scientists named BRAWNIN, have similar features to rare mitochondrial disease in humans. This prompted further studies of the protein to help explain these rare diseases to uncover possible therapeutic targets.

Led by cell and developmental biologist Lena Ho, the team discovered 16 short open reading frame-encoded peptides (SEPs). Its genetic code is translated in the nucleus, which are then imported into mitochondria.

“SEPs have been fascinating the scientific community for several years now, as they represent a mini-proteome that has never been explored; a repository of new gene functions,” said Dr Ho. “But there haven’t been systematic studies to validate their functions and biological relevance. We found that the mitochondria are a hotspot for their functions, for reasons we don’t completely yet understand.”

Singling out one of the 16 mitochondrial SEPs, which was named BRAWNIN, they knocked out the gene that codes for it in zebrafish. Following that it was observed in the zebrafish extreme growth retardation and lactic acid accumulation in cells. Further tests revealed that BRAWNIN was essential for the assembly of a group of molecules in the mitochondria called respiratory chain complex III. According to Dr Ho, this molecular complex is essential for all life forms that use oxygen for energy generation.

“Mitochondrial decline and dysfunction underlie all degenerative diseases and has been widely implicated in cancer,” Dr Ho said. “The proteins we’ve discovered, including BRAWNIN, represent potential targets for reversing mitochondrial decline.”

Following this study, the team will go on to understand the mechanisms behind BRAWNIN in complex III assembly. They are also investigating how BRAWNIN malfunction can affect disease predisposition and how it may be a potential target.

Dr Ho added that the other 15 mitochondrial SEPs will still need to be investigated and are actively looking for collaborators. [APBN]