Researchers Found Two New Types of Mammalian Respirasomes
The biological process of oxidative phosphorylation takes place in the cells of all eukaryotic, aerobic organisms: It produces energy that sustains the life of complex organisms such as humans. Its malfunction is associated with severe diseases, affecting multiple organs, but in particular the brain and muscles.
The oxidative phosphorylation system consists of five molecular machines, also known as complexes I to V (CI, CII, CIII, CIV, CV). They get together and form supercomplexes, among which one is called the “respirasome” and contains complexes CI, CIII and CIV. Irene Vercellino, now group leader at the Institute of Structural Biology (ER-C-3) at Forschungszentrum Jülich, and Leonid Sazanov from the Institute of Science and Technology Austria used powerful electron microscopes to image these supercomplexes and discovered that different respirasomes can form from the same components, differently arranged in the space. These different arrangements might help the cells to finely adapt to the metabolic needs of complex organisms like mammals.
Scientific Results
The researchers found two new types of respirasome, existing in mammalian tissues alongside the canonical respirasome. One of the two new species – the CS-respirasome – contains a protein called SCAF1, which is necessary for the assembly of another protein supercomplex called CIII2CIV. It had previously been debated whether SCAF1 plays a role in respirasome assembly: SCAF1 had been identified by biochemical methods, but it had never been structurally observed. The new findings clarify this debate and show that the reason why SCAF1 had not been observed in previous respirasome structures is that the CS-respirasome is a different supercomplex than the canonical respirasome. There are therefore two distinct types of respiratory chains: One dependent on SCAF1, containing the CS-respirasome and CIII2CIV, and another independent of SCAF1, containing the A-, C-respirasomes and CICIII2.
Social and Scientific Relevance
The presence and abundance of SCAF1 in the body is regulated by estrogens and has been found to be upregulated in various types of cancer. This suggests that the molecular fine-tuning of metabolism, that can be achieved through the formation of different supercomplexes, can have profound effects on the entire organism.
Additional Details
The scientists obtained the supercomplexes from native mouse tissue, which serves as a model for mammalian cells.
Contact
Dr. Irene Vercellino
Group Leader
- Ernst Ruska-Centre for Microscopy and Spectroscopy with Electrons (ER-C)
- Structural Biology (ER-C-3)
Room 4016a
