A new study, recently published in Nature, helps to understand the regulation of our metabolism and provides a breakthrough in understanding the organization of the mitochondrial respiratory chain (in charge of producing energy from ingested nutrients). The results are a major step that will also serve to analyze the relationship of these structures with the risk of developing various diseases.
Researchers at the National Center for Cardiovascular Diseases Carlos III (CNIC), Spain, have molecularly defined how the mechanisms responsible for cellular energy production are organized.
For years, scientists thought that the structures that allow cellular respiration within the mitochondria are arranged randomly. For this reason, there has been a gap in the understanding of mitochondrial respiration and the importance of its regulation in cellular and metabolic stress, as well as its possible role in disease development.
The research carried out by the teams led by José Antonio Enriquez and Jesus Vazquez, and which first authors are Sara Cogiati and Enrique Calvo, has focused on the role of the mitochondrial electron transport chain terminal complex, called complex IV.
It was already known that complex IV is formed by the assembly of 14 proteins, and that our cells can make different versions of some of these proteins. However, the role of these versions was still unknown.
Now the study reveals that the exchange of different versions of the same protein (called SCAF1, Cox7a1 and Cox7a2) acts as a regulatory factor in the formation of different structures. According to Enriquez, “these alternative versions determine the final organization of mitochondrial structures.”
So, what can it be the impact of these different organizations? “Let’s think about children building blocks of different sizes, shapes and structures,” Cogiati explains. “Each of these blocks must be placed in the right place to do the construction, as each of them has a special function. Depending on whether assemble blocks in one way or another, we can get a house, a bridge or a fire station: all are constructions, but with different features and functions.”
Similarly, the mitochondrion organizes its own respiratory chain, i.e. “by using different proteins, different structures are built with slightly different functions,” Calvo said.
“And thanks to our work, we now know that the exchange of alternative forms of SCAF1 protein is a regulatory mechanism that controls the structure and activity of the respiratory chain and, therefore, cell metabolism,” explained Vazquez.
The researchers conclude that these findings, in addition to unravel the mechanisms of organization of mitochondrial respiratory chain, are a major step that will serve to advance in the understanding of how different organizations of the mitochondrial respiratory chain affect metabolism, as well as the relationship of these structures with the risk of various diseases.
Source: Agencia SINC