A newly-discovered small protein in mitochondria is essential for energy production, according to researchers from Duke-NUS Medical School and their collaborators, who recently published a study in the journal Nature Communications. The researchers name the protein BRAWNIN, and when BRAWNIN was found to be lacking in Zebrfish, they had similar features to rare mitochondrial diseases in humans, suggesting that further studies of the protein could help explain these conditions and identify possible therapies.
 
The international research team, led by cell and developmental biologist Lena Ho, an assistant professor at Duke-NUS Medical Schools Cardiovascular and Metabolic Disorders Program, discovered 16 ‘short open reading frame-encoded peptides’ (SEPS) whose genetic code is translated in the nucleus, but which are then imported into the mitochondria, the power-generating structures of the cells.
 
“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,” Dr. Ho said. “But there haven’t been systematic studies to validate their functions and biological relevance. We found that the mitochondria are a hotspot for hteir functions, for reasons we don’t completely yet understand.”
 
The scientists singled out one of the 16 mitochondrial SEPs they discovered for further analysis. Knocking out the gene that codes for BRAWNIN led to extreme growth retardation and lactic acid accumulation in zebrafish cells. Further tests revealed that BRAWNIN was essential for the assembly of a group of molecules in the mitochondria called respiratory chain complex III. This molecular complex is essential for all life forms that use oxygen for energy generation, Dr. Ho said.
 
The team is now trying to understand how exactly BRAWNIN is involved in complex III assembly. They are also investigating which diseases could be predisposed to by BRAWNIN malfunction nad how using the protein might be as a target to reverse their pathologies.
 
“Mitochondrial decline and dysfunction underlies all degenerative diseases and has been widely implicated in cancer,” Ho said. “The proteins we’ve discovered, including BRAWNIN, represent potential targets for reversing mitochondrial decline.”
 
Ho noted that there are 15 more mitochondrial SEPs to investigate, and her team is looking for collaborators who are interested in studying them.