Mitochondria are the cell’s powerhouses, producing most of a cell’s energy needs through an electrochemical process called the electron transport chain, which is coupled to another process known as oxidative phosphorylation. A number of different proteins in mitochondria facilitate these processes, but it is not fully known how these proteins are arranged within the mitochondria and what factors can affect their arrangement.
Now, using the latest proteomics technology, scientists from the University of Copenhagen have shed new light on how mitochondrial proteins assemble into complexes of the electron transport chain and further into so-called super complexes. The research that is published in Cell reportsalso examined how this process is influenced by exercise training.
This study enabled a comprehensive quantification of proteins in the electron transport chain in supercomplexes and their response to exercise training. This data has an impact on how exercise improves the efficiency of muscle production. “
Atul S. Deshmukh, Associate Professor, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen
Traditional methods do not provide enough details
It is already known that exercise training stimulates mitochondrial mass and affects the formation of super complexes, which enables mitochondria in skeletal muscle to produce energy more efficiently. The question remains, however, which complexes combine to form supercomplexes and how.
To better understand the formation of supercomplexes, especially in response to physical activity, the team of scientists studied two groups of mice. One group was active and given an exercise bike for 25 days, and the second group was sedentary and did not receive an exercise bike. After 25 days, they measured the mitochondrial proteins in skeletal muscle in both groups to see how the supercomplexes had changed over time.
Typically, when scientists analyze how supercomplexes form, they use antibodies to measure one or two proteins per electron transport chain complex. However, because a complex can contain up to 44 proteins, this method is both time consuming and provides limited information about what happens to the rest of the proteins in each complex.
As a result, there is a lack of detailed knowledge in this area.
Proteomics helps supercomplexes reveal their secrets
To generate much more detailed data, the team used a proteomic technology called mass spectrometry to measure the mitochondrial proteins. By using proteomics instead of antibodies, the scientists were able to measure nearly all of the proteins in each complex. This provided unprecedented detail on mitochondrial supercomplexes in skeletal muscle and how exercise training affects their formation. Their approach showed that not all proteins in every complex or super complex respond in the same way to exercise.
“It is well known that mitochondrial protein levels increase with exposure, so understanding how these proteins assemble into supercomplexes to understand how they work. Our research is a valuable and valuable resource for science especially for those studying how mitochondrial proteins organize themselves better at what they do best: producing energy as needed, “explains postdoc Alba Gonzalez-Franquesa.
Gonzalez-Franquesa, A., et al. (2021) Mass spectrometric proteomics shows the plasticity of mitochondrial supercomplexomes. Cell reports. doi.org/10.1016/j.celrep.2021.109180.