„Surprising” Discovery – Scientists Identify Complete Respiratory Supercomplex

Every eukaryotic cell contains tiny „powerhouses” called mitochondria, which are responsible for making the all-purpose energy molecule, ATP. To fulfill this role, mitochondria must maintain a spatial arrangement of membrane proteins that mediate various steps in ATP generation.

During the cellular breakdown of sugars, energy is released and used within the mitochondria to generate ATP. This process is centrally dependent on four membrane protein complexes – named complex I, II, III and IV. Collectively, these complexes form an energy gradient that is used by complex V to synthesize ATP. These ATP molecules catalyze a variety of reactions throughout cells, a process critical to sustaining life.

Respiratory complexes I, III and IV interact with each other and are called respiratory supercomplexes, which enhances interactions between the complexes. Until now, researchers have not noticed that complex II is part of a supercomplex. In mammalian mitochondria, supercomplexes are spatially separated from complex V in the membrane, where supercomplexes reside only in membrane regions without curvature. However, there are unicellular eukaryotic organisms Tetrahymena thermophila Whose mitochondria have only curved membranes, so a key question is where the supercomplexes are located in these membrane structures.

Now an international team of researchers with the participation of postdoc Rasmus Kock Flygaard from the Department of Molecular Biology and Genetics[{” attribute=””>Aarhus University, has answered a number of key questions regarding supercomplexes from Tetrahymena.

“For the first time ever, we have shown that complex II can also form part of a super complex, which shows an incredible optimization of the process for ATP formation”, says Rasmus Kock Flygaard. “Furthermore, with our structure, we can see that supercomplexes do not follow a simple plan for construction, but on the contrary, there is a surprising variety, which was not previously thought possible”.

This variation in the structure of the supercomplex is also central to the question of its existence in curved membranes, and Rasmus Kock Flygaard continues:

“The supercomplex from Tetrahymena has been rebuilt and expanded with countless proteins and extra domains, which overall give the supercomplex a curved architecture, so that it is completely adapted and developed to exist in curved membranes. This is an incredible example of how nature is able to adapt otherwise conserved protein complexes to new environments to maintain function. Now, we have investigated the membrane protein structure of a single organism and made completely new discoveries. There are so many more single-celled eukaryotic organisms that are also just waiting to be described, so that we can provide a more nuanced picture of how life has evolved and adapted.”

Reference: “Structural basis of mitochondrial membrane bending by the I–II–III2–IV2 supercomplex” by Alexander Mühleip, Rasmus Kock Flygaard, Rozbeh Baradaran, Outi Haapanen, Thomas Gruhl, Victor Tobiasson, Amandine Maréchal, Vivek Sharma and Alexey Amunts, 22 March 2023, Nature.
DOI: 10.1038/s41586-023-05817-y