Mammalian mitochondrial complex I structure and disease causing mutations Review Article


Author(s): Fiedorczuk, Karol; Sazanov, Leonid A
Title: Mammalian mitochondrial complex I structure and disease causing mutations
Affiliation IST Austria
Abstract: Complex I has an essential role in ATP production by coupling electron transfer from NADH to quinone with translocation of protons across the inner mitochondrial membrane. Isolated complex I deficiency is a frequent cause of mitochondrial inherited diseases. Complex I has also been implicated in cancer, ageing, and neurodegenerative conditions. Until recently, the understanding of complex I deficiency on the molecular level was limited due to the lack of high-resolution structures of the enzyme. However, due to developments in single particle cryo-electron microscopy (cryo-EM), recent studies have reported nearly atomic resolution maps and models of mitochondrial complex I. These structures significantly add to our understanding of complex I mechanism and assembly. The disease-causing mutations are discussed here in their structural context.
Keywords: Respiratory complex I; Cryo-electron microscopy; mitochondrial disease; mitochondrial respiratory chain; NADH–ubiquinone oxidoreductase
Publication Title: Trends in Cell Biology
Volume: 28
Issue 10
ISBN: 09628924
Publisher: Elsevier  
Date Published: 2018-07-26
Start Page: 835
End Page: 867
DOI: 10.1016/j.tcb.2018.06.006
Open access: no