Mitochondria and inflammation and muscle atrophy

Mitochondria—the powerhouses of cells—play an essential role in cell physiology. The union of two or more mitochondria and the division of a mitochondrion into two units are common processes. They are known as mitochondrial dynamics and are necessary for the proper functioning of these structures and of the cell itself.

A recent study, published in the academic journal Nature Communications, describes for the first time a mechanism of cellular inflammation related to alterations in mitochondrial dynamics that leads to muscle atrophy. According to the study’s conclusions, blocking the union of mitochondria or blocking their fragmentation trigger the inflammatory process, although they do so through different mechanisms.

The experts Antonio Zorzano and David Sebastián lead the work. Zorzano is a professor at the Faculty of Biology at the University of Barcelona (UB), head of the Complex Metabolic Diseases and Mitochondria Laboratory of the Barcelona Biomedical Research Institute (IRB Barcelona) and group leader of the Diabetes Network Biomedical Research Center and Associated Metabolic Diseases (CIBERDEM), in Spain. Sebastián is a professor at the Faculty of Pharmacy and Food Sciences, a researcher associated with the IRB and a member of CIBERDEM.

«Chronic inflammation is one of the processes that condition our health, since it is linked to a wide range of diseases such as diabetes, Alzheimer’s, Parkinson’s, cancer and also aging. That is why it is important to understand it, in order to tackle it and prevent related disorders”, explains Zorzano.

This phenomenon has been observed in muscle cell cultures and in muscles of experimental mouse models. The type of inflammation described is known as sterile inflammation, since it is not linked to an infectious process. These studies open the way to explore the role of alterations in mitochondrial dynamics in the development of certain diseases, especially those that affect muscles.

3D reconstruction of mitochondria, endosomes and mitochondrial DNA from a healthy muscle cell. (Image: UB / IRB Barcelona)

The mechanisms that trigger inflammation

“One of the most notable findings of our study is that when we push mitochondrial dynamics towards one of its two extremes (mitochondrial fragmentation or elongation), these inflammatory pathways are activated in different ways. In both cases, yes, the activation of these pathways involves the recognition of mitochondrial DNA by intracellular DNA sensors”, explains Andrea Irazoki, co-author of the study, from the Faculty of Biology of the UB, the IRB and the CIBERDEM, and currently a postdoctoral researcher at the University of Copenhagen (Denmark).

“In that work, we have discovered an essential role for inflammatory mitochondrial dynamics. Together with previous results from the group that show alterations in the dynamics during aging, these new findings could explain the increase in inflammation associated with aging,” says David Sebastián, head of the Mitochondria, Metabolic Diseases and Aging laboratory. (Source: UB)