The respirasome, comprising multiple protein complexes, facilitates electron transfer and ATP production, which is the primary energy source for cells. While the aggregation of these complexes into larger structures was known, the precise mechanism of their assembly, whether as fully formed units or through a stepwise process, remained undefined.
Researchers at the Department of Medical Biochemistry and Biophysics utilized high-resolution cryo-electron microscopy to identify previously unobserved intermediates in the respirasome assembly. These findings suggest that the final assembly stages occur concurrently with the maturation of Complex IV, a crucial component. This implies that the respirasome may serve as a framework to guide the sequential order of its own assembly.
Furthermore, the study identified HIGD2A as a temporary protein within Complex IV. This protein occupies a critical site until the incorporation of the final subunit, NDUFA4. This mechanism ensures that the respirasome achieves its functional configuration in a controlled sequence.