Sergio Guererro, Fabian Baertling and colleagues from the Radboud Center of Mitochondrial Medicine (RCMM) elucidated the assembly pathway of the 44 subunit containing mitochondrial complex I. This work has recently been published in the scientific journal “Cell Metabolism”.
Mitochondrial complex I is a key metabolic enzyme as it is the major entry-point of electrons in the respiratory chain. It oxidizes NADH and pumps protons across the inner membrane to provide the driving force for complex V to make ATP. In addition, this enzyme is the major producer of reactive oxygen species and defects in this enzyme are the most frequent cause for inherited mitochondrial disorders. Furthermore, complex I dysfunction has been implicated in Parkinson’s and Alzheimer’s disease as well as in cancer development and ageing. To understand how this complex is regulated and how mutations lead to disease, it is vital to understand how the 44 different subunits are assembled and which factors are required in this process.
The RCMM groups of Leo Nijtmans, Susanne Arnold and Ulrich Brandt teamed up to tackle this problem. They used their recently developed dynamic complexome profiling approach “complexomics” to solve the whole assembly pathway of complex I. The stepwise incorporation of all subunits mirrors the evolutionary origin of the complex, it shows that the complex I assembly is completed before it associates with other respiratory complexes and it reveals three novel putative complex I assembly factors.
In addition, the article also illustrates the awesome power of the complexomics approach as it can be used to disclose a complete biochemical pathway.
Sergio Guerrero-Castillo, Fabian Baertling, Daniel Kownatzki, Hans J. Wessels, Susanne Arnold, Ulrich Brandt and Leo Nijtmans; The Assembly Pathway of Mitochondrial Respiratory Chain Complex I; Cell Metabolism, DOI: 10.1016/j.cmet.2016.09.002.