The study was published in the September 22 advance online edition of The American Journal for Human Genetics during mitochondrial disease awareness week.
For 30 years, researchers have been working to better understand mitochondrial diseases.
Mitochondrial diseases are a result of a genetic mutation that causes these energy-producing structures to fail to produce energy. Without this energy, the affected cells die and the body is no longer able to power its organs causing a variety of health problems such as muscle weakness, high acidity in the body and degeneration of the central nervous system.
Iron-sulfur clusters are an electron-conducting unit that generates energy to produce life and plays an essential role in mitochondria.
“There has been considerable interest in how iron-sulfur clusters are formed,” says Dr. Brian Robinson, Senior Scientist in Genetics & Genome Biology at SickKids. “It has been known that two cellular pathways, the NFU and ISCU pathways, are involved in iron-sulfur cluster assembly, but the ISCU pathway was thought to be more important.”
Scientists identified two distinct genetic defects in two families with mitochondrial disease. Both genes were found on the NFU pathway. The defective genes affected the process by which the iron-sulfur clusters were assembled in the mitochondria.
“The identification of the defective genes, NFU1 and BOLA3, on the NFU pathway suggests that this pathway is more important for the assembly of iron-sulfur assembly than we thought,” explains Robinson, who is also Professor in Biochemistry & Paediatrics at the University of Toronto. “Prior to this study, no defects had been identified on the NFU pathway. The discovery of these genes shows that there are more severe consequences for iron-sulfur cluster assembly on the NFU pathway.”