Mitochondrial complex I activity in microglia sustains neuroinflammation. (https://pubmed.ncbi.nlm.nih.gov/38480879/)

These scientists wanted to understand why some diseases that affect the brain and spinal cord, like multiple sclerosis, have cells that stay active and cause inflammation for a long time. They found that certain features in these cells, called myeloid cells, are linked to their activation and the different jobs they do in the body. But they didn't know exactly how these features keep the inflammation going in the central nervous system.

So, the scientists decided to study this using a lot of different methods, like looking at the genes and molecules in these cells. They discovered that a specific process happening in the mitochondria of the cells, called complex I activity, was driving the production of harmful substances that can damage the brain and spinal cord.

To test this idea, the scientists blocked complex I in these cells that were causing inflammation. They found that by doing this, they could protect the nervous system from getting damaged and improve how well the animals with the disease were feeling.

This study suggests that targeting complex I activity in these cells could be a way to help protect the brain and spinal cord in diseases where inflammation is a big problem.

Peruzzotti-Jametti L., Willis CM., Krzak G., Hamel R., Pirvan L., Ionescu RB., Reisz JA., Prag HA., Garcia-Segura ME., Wu V., Xiang Y., Barlas B., Casey AM., van den Bosch AMR., Nicaise AM., Roth L., Bates GR., Huang H., Prasad P., Vincent AE., Frezza C., Viscomi C., Balmus G., Takats Z., Marioni JC., D'Alessandro A., Murphy MP., Mohorianu I., Pluchino S. Mitochondrial complex I activity in microglia sustains neuroinflammation. Nature. 2024 Apr;628(8006):195-203. doi: 10.1038/s41586-024-07167-9. Epub 2024 Mar 13.