• Cecilia Hägerhäll

Complex I, or NADH:quinone oxidoreductase, catalyzes the first step in the respiratory chain. Although the complete structure of the enzyme complex have now been solved (see PDB file 4HEA) the functional mechanism remains poorly understood. The classical Complex I enzyme is composed of seven membrane-spanning protein subunits and seven protein subunits protruding into the cytoplasm (in bacteria) or into the mitochondrial matrix (in eukaryotes). Complex I from eukaryotes also contain up to 32 additional accessory subunits. The NADH binding site, FMN and eight FeS clusters are located in the promontory part, whereas the seven membrane-spanning proteins are all encoded by mitochondrial DNA in eukaryotes, in fact the Complex I encoding genes make up half of the mtDNA in mammals. This results in that Complex I is both a victim of free radical damage and a main culprit in generating such radicals. Defect complex I is associated with many degenerative diseases, and thus further understanding of complex I is of great medical importance. By better understanding of how the evolutionary forces that formed the enzyme complex operated, we will also learn how the modern enzyme works. Our hypothesis is that the recruitment of the Mrp-antiporter is a key event in complex I evolution, that happened not just once but twice. If you want to read more about this, go here!

Find out more about Complex I, and the people working on this topic at

The Complex I web page

Our overall goal is to understand how complex I works on the molecular level. Therefore, in the lab we working with molecular biological approaches such as making mutants and fusion proteins but also purely biochemical/biophysical projects, purifying proteins for reconstitution into liposomes, where the ion translocation activities can be measured by Na+ NMR using a shift reagent or by a pH sensitive, membrane-impermeable dye denoted Glu3.