A new study shows how one of the cell’s most important energy-producing machines is built. Researchers at Karolinska Institutet have mapped late steps in the formation of the human respirasome, a large protein assembly that drives mitochondrial respiration. Their research is published in the journal Nature Communications.

The respirasome is made up of several protein complexes that work together to transfer electrons and support the production of ATP, the cell’s main energy source. Although scientists have known that these complexes can join to create larger structures, it has remained unclear whether they assemble as finished units or form step by step.

Using high-resolution cryo-electron microscopy, the research team at the Department of Medical Biochemistry and Biophysics captured previously unknown intermediates of the respirasome. Their findings suggest that the final stages of assembly occur while one of the key components, complex IV, is still maturing. This indicates that the respirasome may act as a platform that helps guide the correct order of assembly.