Our field of interest
Our goal is to understand how energy is transduced in biological systems from a molecular perspective as well as from a cellular point of view as integrated in energy metabolism. Our studies involve isolated proteins (wild type and recombinants) as well as reconstituted proteins or membrane vesicles and cell fitness and metabolomic analyses, resulting, in this way, in a synergy of molecular and cellular approaches.
The research in the group expands along two main axes:
1
Unveiling the mechanisms of energy transduction by charge translocating membrane proteins
Energy transduction is at the basis of life. Cells utilize different forms of energy, ATP, or electrochemical membrane potentials, for solute import, build of their components and motility. In living cells most energy is transduced by membrane proteins of the electron transfer chains during the processes of cellular respiration or photosynthesis. In these complexes the thermodynamic favorable electron transfer is coupled to the thermodynamic unfavorable translocation of ions across the cytoplasmatic membrane, and the energy thus released by the electron transfer is transduced to the form of a transmembrane difference of electrochemical potential. This transmembrane potential is vital for solute/nutrient cell import, synthesis of ATP and motility (Figure 1). Peter Mitchell proposed the existence of such potential for the first time in his Chemiosmotic Theory.
Energy transduction. Schematic representation of a cell membrane (in grey) containing energy transducing membrane protein complexes. These membrane proteins contribute to the establishment of a transmembrane difference of the electrochemical potential () by coupling the Gibbs energy change (), involved in chemical (a) or light (b) reactions, to the thermodynamically unfavorable translocation of charges (electrons/ions) across the membrane (solid blue arrows). One side of the membrane is referred as being negative (-) and the other positive (+). can drive different cellular processes (dashed blue arrows), such as the synthesis of ATP (c), transport of solutes across the membranes (solid black arrow) (d) and flagellar movement (e).
We have been exploring different energy transducing respiratory enzymes, namely their structural features and catalytic characteristics enabling to dissect molecular mechanisms of electron transfer, ion translocation and their coupling. We have been tackling the operational mechanisms of the respiratory alternative complex III, ACIII.
2
Dissecting the role of non-energy transducing respiratory proteins – Monotopic quinone reductases
We have also been scrutinizing non-energy transducing complexes. These enzymes, for example Complex II from mitochondrial respiratory chain, do not directly contribute to the establishment of the membrane potential, but produce metabolites, e.g., quinol, which are substrates of energy transducing enzymes. We have been studying monotopic quinone reductases from Staphylococcus aureus and Pseudomonas aeruginosa monotopic enzymes, two opportunistic pathogens and two major public health threats due to the increased incidence of their drug resistance.
