Energy production in living organisms must always run smoothly
Mutations can lead to serious diseases
Proton pump I
Complex I is the first enzyme of the respiratory chain and has a central role in cellular energy production, coupling electron transfer between NADH and quinone to proton translocation by an unknown mechanism. Dysfunction of complex I has been implicated in many human neurodegenerative diseases. Complex I has also been suggested to be a major source of reactive oxygen species in mitochondria, which can damage mitochondrial DNA and may be one of the causes of Parkinson’s disease and ageing.
Structure of complex I
In this study, the structure of complex I from the aerobic yeast Yarrowia lipolytica was solved by electron cryo-microscopy (cryo-EM) at high resolution of 3.2 Å. Thus, a substrate molecule could be identified in the access path to the active center and the structure indicated an unusual lipid-protein arrangement at the membrane transition. Furthermore, the structure of a complex I assembly intermediate and mutant (structure solved at 4.0 Å resolution) provide detailed molecular insights into complex I assembly and the cause of a hereditary complex I–linked disease, which has been shown to cause the Leigh's disease in humans with various types of mutations. Patients have a homogeneous phenotype characterized by early onset of the disease and clinical presentation of hypotension, psychomotor regression, abnormal eye movements and respiratory failure in combination with brain stem and basal ganglia lesions leading to death.