Study published in PNAS contradicts belief that this import was possible only in lower organisms.
New research is reversing the belief that only in lower organisms can tRNAs be imported to the mitochondria from the cell cytoplasm, according to a group of scientists. They found that this transfer occurs in rat liver cells and human cells as well.
“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 from the cytoplasm into the mitochondria and correct the malfunction,” says Juan Alfonzo, Ph.D., senior author of the study and an assistant professor of microbiology at Ohio State University.
Since there appears to be no way to introduce healthy tRNAs directly into mitochondria, and it was unknown that human mitochondria had this import ability, researchers were trying to use protozoan or yeast cells to manipulate the import process in human cells. “What we are saying is you don’t need to bring up new machinery from a different organism, because human cells already come equipped with their own way to import tRNAs,” Dr. Alfonzo remarks. “What we need to know now is what proteins are involved in the import mechanism so we can exploit the process for therapy.”
The research team demonstrated ATP’s role in the process using cells from a patient with a specific type of epilepsy called MERRF. This disease is characterized by a mitochondrial tRNA mutation leading to a drastic reduction in the mitochondria’s ability to generate ATP, which in turn hinders the import of tRNAs into the mitochondria.
When ATP was introduced to the mitochondria of these diseased cells, the import process of tRNAs from the cytoplasm to the mitochondria was restored. “These were cells from an actual patient, so this also makes the argument that we don’t need a surrogate system from other organisms to set the import process in motion,” Dr. Alfonzo reports.
Investigators from Ohio State University’s department of microbiology, Yale University’s departments of molecular biophysics and biochemistry and chemistry, and the Institute for Physiological Chemistry at Ludwig-Maximilians-University in Munich all contributed to the research. The research appears online in Proceedings of the National Academy of Sciences.
