Structural insights into the role of mitochondrial complex I in heart attack

Zhan Yin

A collaborative research project led by Professor Judy Hirst at the MBU, working with Mike Murphy (MBU) and Thomas Krieg (Medicine), provides important new insights into the cell damage that occurs during heart attacks. This work, published in Nature Communications with MBU PhD student Zhan Yin as first author, focuses on a version of mitochondrial complex I that contains a single amino acid mutation. Intriguingly, this mutation blocks reactive oxygen species (ROS) production by the complex. Furthermore, the CryoEM structure of the complex provides mechanistic insight into how the mutation blocks ROS production. Remarkably, the lack of damaging ROS production by mutated complex I protected mice from cardiac damage during heart attack. These results provide compelling support for the central pathological role of complex I in heart attack and emphasise its potential as a therapeutic target.

Publication reference: Yin, Z., Burger, N., Kula-Alwar, D., Aksentijević, D., Bridges, H. R., Prag, H. A., Grba, D. N., Viscomi, C., James, A. M., Mottahedin, A., Krieg, T., Murphy, M. P. & Hirst. J. (2021) Structural basis for a complex I mutation that blocks pathological ROS production. Nat Commun 12, 707

This publication is featured in the Editors’ Highlights webpage of recent research called “Structural biology, biochemistry and biophysics”.