• Arvo (3rd floor), Lääkärinkatu 1, 33520 Tampere, Finland
 
 
 
 
 

Brendan Battersby

Brendan4

 

People

Publications

The ability to use oxygen in our bodies is derived from the presence of the small, but dynamic organelle in the cell known as the mitochondrion. Since the organelle is always more than one within the cell we usually refer to the plural, mitochondria. All nucleated cells contain mitochondria but how a cell coordinates the maintenance and biogenesis of this essential organelle is very poorly understood. Research in my laboratory is dedicated to elucidating the mechanisms responsible for this intracellular communication.

Mitochondria contain their own genome and distinct set of ribosomes for the synthesis of only 13 (in mammals) proteins that are components of the oxidative phosphorylation complexes required for aerobic energy metabolism. These complexes are embedded in the inner membrane of mitochondria and composed of over 80 individual proteins, so the majority of the proteins are encoded in the nucleus, synthesized on cytosolic ribosomes and then imported into mitochondria. Thus, assembly of the oxidative phosphorylation complexes requires temporal and spatial coordination from two genomes and two sets of ribosomes.

Mitochondrial ribosomes have evolved to translate only 13 (in mammals) proteins, which make them the simplest protein synthesizing machinery in biology. Ribosomes are composed of protein and nucleic acid (rRNA) and in this respect mitochondrial ribosomes are distinct from those in all Domains of life having much more protein and less rRNA. Nonetheless, the steps of protein synthesis on mitochondrial ribosomes are very similar to that seen in prokaryotes and reflect the alpha-proteobacterial ancestry of this organelle. A consequence of this is that certain classes of antibiotics used against prokaryotes can also impair mitochondrial protein synthesis as a side effect.

Disruptions to mitochondrial protein synthesis by genetic mutation or pharmacologically can have profound effects to organellar and cellular fitness, so that chronic perturbations in the system manifest as human disease. It is often assumed that the greatest impact from impaired mitochondrial protein synthesis is the actual loss of the oxidative phosphorylation complexes per se, so that a defect in the production of the cellular energy carrier ATP exclusively accounts for the disease phenotypes. The problem is the data supporting this interpretation is lacking and it also fails to acknowledge the thousands of upstream molecular events that are required to actually synthesis proteins, any one of which could be major modifier to human disease and a compounding factor to the defect in energy metabolism. Research in my laboratory has been seeking to uncover the molecular mechanisms that link disruptions to mitochondrial protein synthesis to human disease.

We have shown for the first time how disruptions to mitochondrial protein synthesis can generate a membrane stress that triggers a retrograde signalling cascade to the cytosol and then to the nucleus as part of a biological circuit monitoring mitochondria. This circuit is at work in all cells and how disruptions to it manifest in different human cell types is the current subject of our research. Our goal is to identify all of the molecular components of this circuit and decipher how they are integrated and function.

The outcome of our research findings has two important implications to human disease. On the one hand disruptions to mitochondrial protein synthesis are increasingly being identified as a genetic basis for inherited human disorders, so our research helps in elucidating the pathogenesis that is required for the development of therapies. While on the flip side, triggering stress to mitochondrial protein synthesis with specific classes of antibiotics in the short term can be advantageous in the treatment of aberrantly proliferating cells, that is cancer. The latter option is actively being pursued internationally but the precise molecular mode of action for many of these drugs is still lacking and required to optimize this therapy approach.

To find out further information on research in my laboratory please contact me by email.


Contact information
Brendan Battersby, docent, PhD
Institute of Biotechnology
P.O Box 56
Visiting address: Viikinkaari 5d
00014 University of Helsinki
This email address is being protected from spambots. You need JavaScript enabled to view it.