Scientists from the University of Freiburg and the University of Frankfurt have elucidated the architecture of the biggest protein complex of the cellular respiratory chain. They discovered in this molecular complex a previously unknown energy conversion mechanism, which is essential for the cell to be able to utilise the energy contained in food.
After ten years of research, X-ray crystallographic analysis of the biggest and most complicated protein complex of the mitochondrial respiratory chain was finally successful. This protein complex consists of more than 40 different proteins and is the entry point of cellular respiration, which is why it is also referred to as mitochondrial complex I. The results have been published in the current online edition of the scientific journal Science.
A detailed understanding of the function of complex I is of particular medical interest, as dysfunctions of the complex are associated with a number of neurodegenerative diseases such as Parkinson's and Alzheimer's diseases, as well as with the physiological processes of ageing in general. Work carried out by Prof. Carola Hunte of the Freiburg Institute for Biochemistry and Molecular Biology and the Freiburg excellence cluster BIOSS (Centre for Biological Signalling Studies) in cooperation with Prof. Ulrich Brandt, Professor of Molecular Bioenergetics and member of the "Macromolecular Complexes" excellence cluster, and his research group colleague, Dr. Volker Zickermann, is a major step towards achieving the necessary understanding.
The energy metabolism takes place in what are known as the powerhouses of the cell, the mitochondria. They transfer the energy taken up as food into adenosine triphosphate, or ATP, which is the universal energy currency of life. A chain of five complicated machines in the mitochondrial membrane is responsible for the energy conversion. The reason why the production of ATP in the mitochondria requires such a large number of steps is because the underlying conversion corresponds to a Knallgas reaction. The reaction of hydrogen and oxygen in the laboratory leads to an explosion resulting in the contained energy being released as heat. In biological oxidation, the energy is released in small packages by the membrane-bound protein complexes of the respiratory chain in a controlled manner. In a similar way to a fuel cell, this process generates an electrical membrane potential, which is the driving force for the synthesis of ATP. The total surface of mitochondrial membranes in the human body stretches over approximately 14,000 square metres and around 65 kg of ATP are produced each day.
The structural model published in Science provides important and unexpected insights into the function of complex I. A special type of molecular “transmission element” which is not known in any other protein appears to be responsible for the transduction of energy within the complex by way of mechanical nanoscale coupling. Transferred to the world of technology, this could be likened to the power transmission of coupling rods that join the wheels of a steam train. This new nanomechanical principle will now be analysed in functional studies and refined structural analyses.
Further information:Prof. Dr. Carola HunteInstitute for Biochemistry and Molecular BiologyBIOSS Professorship for Biochemistry and Structural BiologyUniversity of FreiburgTel.: +49 (0)761/203-5279Fax: +49 (0)761/203-5253E-mail: carola.hunte(at)bioss.uni-freiburg.de