New insights into biological energy conversion

High-resolution structure and dynamics of mitochondrial complex I

November 13, 2021

The supply of the cells with energy is an essential process in all forms of life. Respiratory complex I plays a central role in aerobic energy metabolism but its molecular mechanism is still largely unknown. In a new study using cryo-electron microscopy and computer simulations, researchers at the Max Planck Institute of Biophysics and the Goethe University in Frankfurt am Main, together with colleagues at the University of Helsinki provide a high-resolution structure and computer simulations of this key component of biological energy conversion.

Cryo-EM structure of complex I from Yarrowia lipolytica at 2.1 Å resolution: Mitochondrial NADH:ubiquinone oxidoreductase (complex I) is the largest and most intricate membrane protein complex of the respiratory chain. Complex I couples the transfer of electrons from reduced nicotinamide adenine dinucleotide (NADH) to ubiquinone with the translocation of protons across the inner mitochondrial membrane.

All life processes require a constant supply of energy. ATP (adenosine triphosphate) is formed in specialized organelles of the cell called mitochondria and serves as the cell's molecular fuel. Mitochondrial complex I (NADH:ubiquinone oxidoreductase) is a very large 1-MDa membrane protein complex that forms the starting point of the so-called mitochondrial respiratory chain that generates the driving force for ATP synthesis.

The research team has gained new insights into how complex I functions: Using cryo-electron microscopy, they were able to determine the molecular structure with unprecedented resolution. Proton transfer reactions along chains of water molecules and certain amino acid side chains play a central role in the function of complex I. The excellent quality of the structural data made it possible to precisely localise water molecules in the protein structure and to draw conclusions about the proton transfer pathways. The high-resolution structural data were used for extensive computer simulations to capture the dynamics of the complex. The results were published in the journal Science Advances and provide a new and detailed picture of how a molecular machine works.

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