A new study sheds light on how mitochondrial proteins are synthesized, providing new targets to fight childhood neurological diseases
By Josh Baxt
Photography by Tom Salyer
itochondria make multicellular life possible. These tiny organelles convert glucose into energy, making them critically important for cell survival. Dysfunctional mitochondria can cause devastating diseases, frequently with childhood onset, but until recently they have been difficult to study.
Now, in a paper published as the cover story in the February 19 issue of the journal Science, an international team, including researchers from the Miller School of Medicine and colleagues Alexey Amunts, Ph.D., associate professor of biochemistry and biophysics at Stockholm University in Sweden, and Brendan Battersby, Ph.D., a principal investigator in the Institute of Biotechnology at the University of Helsinki in Finland, has delineated several structures associated with mitochondrial protein synthesis. These findings could help scientists understand the mechanisms that go wrong in some of the deadliest mitochondrial diseases, as well as offer potential therapeutic targets.
“Many of these diseases are embryonically lethal,” said Antonio Barrientos Ph.D., professor in the departments of Neurology and Biochemistry and Molecular Biology and co-lead author on the study. “Even if the kids are born, they often die after only a few years. Now, we have uncovered a basic mechanism that drives pediatric mitochondrial disease.”
An ancient story
The study revolves around a protein called OXAIL-1, which binds to the protein-making machinery and shepherds completed proteins into the mitochondrial membrane. This is a critical step. Because these proteins are hydrophobic, they can only be effective in the lipid (fatty) membrane. If OXAIL-1 doesn’t do its job, mitochondrial proteins remain in water, lose their shape and become useless.
A good fit