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Alterations in mitochondrial dynamics lead to inflammation and muscle atrophy

3d reconstruction of mitochondria (in blue), endosomes (white) and mitochondrial DNA (orange) from a healthy muscle cell.

3d reconstruction of mitochondria (in blue), endosomes (white) and mitochondrial DNA (orange) from a healthy muscle cell.

From left to right, the experts Antonio Zorzano and David Sebastián.

From left to right, the experts Antonio Zorzano and David Sebastián.

18/01/2023

Recerca

Mitochondria —the energy powerhouses of cells— play an essential role in cell physiology. The joining 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 paper published in the journal Nature Communications describes for the first time a mechanism of cellular inflammation linked to alterations in mitochondrial dynamics that leads to muscle atrophy. According to the study, blocking the binding of mitochondria and blocking their fragmentation triggers the inflammatory process, albeit by different mechanisms.

The study is led by Antonio Zorzano, professor at the Faculty of Biology, head of the Complex Metabolic Diseases and Mitochondria Laboratory at the Institute for Research in Biomedicine (IRB Barcelona) and group leader of the Diabetes and Associated Metabolic Diseases Networking Biomedical Research Centre (CIBERDEM), and David Sebastián, professor at the Faculty of Pharmacy and Food Sciences, associate researcher at IRB and 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 ageing. This is why it is important to understand it, so we can reduce it and prevent its related disorders”, says Antonio Zorzano, member of the Department of Biochemistry and Molecular Biomedicine.

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

Mechanisms that trigger inflammation

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

“In this study, we have discovered an essential role for inflammatory mitochondrial dynamics. Together with our group’s previous results which showed alterations in dynamics during ageing, these new findings could explain the increase in inflammation associated with ageing”, notes David Sebastián, head of the Mitochondria, Metabolic Diseases and Ageing lab.

Further information

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