Scientists discover the way cells replace damage to their ‘power-plants’
4 August 2008
Mitochondria are the ‘power-plants’ inside cells that produce the main source of chemical energy, adenosine triphosphate (ATP), that fuels cell function. A crucial part of the process is played by a molecule known as a tRNA, which assembles the proteins used to make ATP inside the mitochondria.
If the genes that encode mitochondrial tRNA are defective or missing, proteins are not manufactured and the mitochondria are unable to generate adequate energy. The range of problems this can create includes hearing loss, diabetes and a number of neurological disorders.
“If you have a mutation in a tRNA that you suspect is involved in disease, you theoretically should be able to bring a healthy tRNA into the mitochondria and correct the malfunction,” said Juan Alfonzo, senior author of the study and an assistant professor of microbiology at Ohio State University.
Previous research has found that simple organisms such as singled-celled protozoa, algae and yeast have their own in-built system to replace mutated tRNAs. Now the Ohio team has discovered that under certain conditions human mitochondria can replace tRNA too. In a patient with defective tRNA, introducing ATP into the mitochondria stimulated cells to restart the ATP production cycle. Healthy tRNAs were then imported from fluid in the cells across the mitochondrial membrane to the inside, enabling them to produce even more ATP.
The discovery brings us closer to treatment for disorders involving mutations in tRNA. “This was totally unexpected, to find an innate, built-in mechanism that we humans have,” added Dr Alfonzo. “What we need to know now is what proteins are involved in the import mechanism so we can exploit the process for therapy.”
Several mutations associated with sensorineural hearing loss have been identified in the gene encoding tRNA, making the condition a target for future tRNA therapies. Similarly, mutations in the mitochondrial genome are also implicated in age-related hearing loss, which affects more than half of people over the age of 65.
