Surprising findings on the energy production in cells
New findings change the idea scientists had for 20 years on the role and importance of the protein MTERF1 in mitochondrial biology. For the first time, a research team at Karolinska Institutet and Max Planck Institute for Biology of Ageing has investigated in vivo what was up to now only explored in cell culture. In experiments on mice, they made a surprising discovery: MTERF1 does after all not play the key role in mitochondrial transcription and translation that was hitherto ascribed to it.
The findings, which are published in the scientific journal Cell Metabolism, will change the way we look at the regulation of mitochondrial function in the cell. With this study, the researchers also demonstrates the way science often works: Long-standing research findings might be overthrown by surprising new insights, thus necessitating future projects with regard to related questions to take on a whole new direction.
"We were very surprised when we didn't get the results that everyone expected. At first we thought that something was wrong with our experiments, and only after conducting many control experiments we became convinced that our results in fact were correct", says Nils-Göran Larsson, Professor at the Department of Laboratory Medicine at Karolinska Institutet, and also Director of the Department of Mitochondrial Biology at the Max Planck Institute for Biology of Ageing in Cologne, Germany.
Proteins are the 'work horses' of an organism. They perform a variety of different processes, for instance regulating genes, controlling metabolism or making cells perform specialized functions. MTERF1 is such a work horse, carrying out its tasks in the mitochondria, also known as the power houses of the cell since they supply energy by converting components in the food we eat to ATP.
While the genetic blueprint of a living organism is largely held in the cell nucleus, the mitochondria carry their own hereditary information, also in the form of DNA. In this context, MTERF1's special role is to act as a mitochondrial transcription termination factor. It defines the right stopping place when it comes to transcribe a section on the DNA into RNA. RNA in turn delivers the genetic information to the ribosomes, which can be described as the 'protein-making factories' of the cell; They synthesize proteins according to the instructions held by the RNA.
Up to now, the role of MTERF1 was only investigated in vitro, using cell culture. And for two decades, this protein was thought to play a crucial role in the regulation of transcription, eventually acting as a key regulator for mitochondrial protein synthesis in mammals. However, by engineering an appropriate mouse model for the first time, the researchers have now learned that this is not the case. According tot he researchers this shows that in vitro systems like cell culture can only to a certain extent represent a natural physiological condition, and that consequently the insights gained in vitro must always be verified in vivo.
The study was funded by the Swedish Research Council, the European Research Council, and the Foundation BLANCEFLOR Boncompagni-Ludovisi, née Bildt. The majort part of this news article has originally been published as a press release by the Max Planck Institute for Biology of Ageing.
MTERF1 binds mtDNA to prevent transcriptional interference at the light-strand promoter but is dispensable for rRNA gene transcription regulation.
Cell Metab. 2013 Apr;17(4):618-26