Mitochondrial complex II is a four-subunit protein machine located in the mitochondrial membrane that links two essential cellular energy-producing processes. Defects in complex II — because of mutations in the genes encoding the subunits or incorrect assembly of the mature complex — are associated with severe disease phenotypes.
Tina Iverson, PhD, and colleagues investigated assembly of human complex II using biochemical analyses and structural studies.
They report in the Proceedings of the National Academy of Sciences an X-ray structure of human SDHA (one of the complex II subunits) and its dedicated assembly factor SDHAF2. They identified a small molecule carboxylate that works with SDHAF2 to properly orient and organize the active site of SDHA for attachment of the flavin cofactor that is critical to complex II function.
The researchers also analyzed the impact of disease-associated SDHA mutations on assembly and identified distinct conformations of SDHA with roles in complex II assembly and catalysis.
This research was supported by National Institutes of Health grant GM061606.