Investigating the role of cytochrome c oxidase and its association in supercomplexes in regulating mitochondrial respiratory chains

Amandine Marechal (primary)
Structural and Molecular Biology
University College London
Giulia Zanetti (secondary)
Biological Sciences


Cytochrome c oxidase or complex IV (CIV) is the terminal enzyme of our respiratory chains. It is a large membrane protein (200kDa) composed of 14 subunits. Three are encoded by the mitochondrial DNA and form the catalytic core but the function of the eleven other subunits, which are nuclear DNA encoded and unique to mitochondrial forms of the enzyme, remain unknown. Of particular interest are evidences for roles in supercomplex formation and allosteric regulation of CIV core catalytic activity. We will address these key questions using a combination of biochemical, biophysical and structural techniques on mitochondrial enzymes from different sources.


1. Rich P.R., Maréchal A. (2010) The mitochondrial respiratory chain. Essays in Biochemistry 47, 1-23.
2. Hartley A.M. et al (2020) Rcf2 revealed in cryoEM structures of hypoxic isoforms of mature mitochondrial III-IV supercomplexes. Proc. Nat. Acad. Sci. USA 117 (17), 9329-9337.
3. Hartley A.M et al (2019) Structure of yeast cytochrome c oxidase in a supercomplex with cytochrome bc1. Nat. Struct. Mol. Biol. 26 (1), 78-83.
4. J. A. Letts JA et al (2016) The architecture of respiratory supercomplexes, Nature 537, 644-648.
5. Milenkovic D et al (2017) The enigma of the respiratory chain supercomplex, Cell Metab 25 (4), 765-76.

Molecules, cells and industrial biotechnology
Area of Biology
Structural Biology
Techniques & Approaches
BiochemistryBioinformaticsBiophysicsChemistryImage ProcessingMathematics / StatisticsMicroscopy / ElectrophysiologyMolecular BiologySimulation / Modelling