Researchers have found that an essential cell protein plays a key role in shuttling RNA into the mitochondria, the energy-producing "power plant" of the cell.
Scientists at UCLA's Jonsson Comprehensive Cancer Center and the departments of Chemistry and Biochemistry and Pathology and Laboratory Medicine, conducted the above study.
The import of nucleus-encoded small RNAs into mitochondria is essential for the replication, transcription and translation of the mitochondrial genome, but the mechanisms that deliver RNA into mitochondria remain poorly understood.
In the current study, UCLA scientists show a new role for a protein called polynucleotide phosphorylase (PNPASE) in regulating the import of RNA into mitochondria.
Reducing the expression of PNPASE decreased RNA import, which impaired the processing of mitochondrial genome-encoded RNAs.
Reduced RNA processing inhibited the translation of proteins required to maintain the electron transport chain that handles oxygen to produce energy in the form of adenosine triphosphate, the energy currency of a cell.
With reduced PNPASE, unprocessed mitochondrial RNAs accumulated, protein translation was inhibited and energy production was compromised, leading to stalled cell growth.
"This discovery tells us that PNPASE regulates the energy producing function of mitochondria by mediating cytoplasmic RNA import. The study yields new insight for how cells function at a very fundamental level. This information provides a potential new pathway to control mitochondrial energy production and possibly impact the growth of cells, including certain types of cancer cells," said Dr. Michael Teitell, co-senior author of the study.
The study could have implications for studying and treating certain cancers, which rely on cellular energy to grow and spread, as well as mitochondrial disorders such as neuromuscular diseases.
The study could also result in new ways to think about attacking neurodegenerative disorders, such as Parkinson and Alzheimer diseases, which have recently been linked to the function of mitochondria.
Carla Koehler, co-senior author of the study said: "This new and novel pathway for transporting RNA into the mitochondria is shedding new light on the evolving role and importance of mitochondria function in normal physiology and a wide variety of diseases. If we can understand how this pathway functions in healthy cells we could potentially uncover defects that help in transforming normal cells into cancer cells."
The study appears in the peer-reviewed journal Cell.