Mitochondria release for restoring cellular function

Healthy mitochondria are essential for the proper function of our cells, and their dysfunction is increasingly recognized as major driver of chronic cardiovascular disease. When these cellular organelles fail, they generate signals that fuel inflammation and disrupt the normal balance of the immune system. During atherosclerosis development, stress-damaged mitochondria accumulate and drive inflammation and disease progression. Macrophages normally maintain homeostasis by removing defective mitochondria. They can either recycle them inside the cell or package them into small vesicles and release them into the surrounding tissue. However, it is still largely unknown how macrophages decide between these two routes and how this decision changes during atherosclerosis. This project addresses this knowledge gap by investigating how macrophages recognise damaged mitochondria, how they decide between recycling and release, and which molecular signals guide this decision. Using advanced experimental models in both humans and mice, we will follow how mitochondria move, change and are disposed of when cells are exposed to stress and pro-atherogenic signals. In parallel, we will screen a large panel of mitochondria-targeted compounds to identify substances that can influence this quality-control system and investigate how such treatments affect inflammation and plaque stability during atherosclerosis development. By uncovering how macrophages sense, sort and eliminate dysfunctional mitochondria, this project aims to reveal a previously unrecognized quality-control mechanism that links altered cell metabolism to chronic vascular inflammation. Understanding and targeting this dual pathway may help restore mitochondrial health, dampen harmful inflammation, and ultimately slow or prevent the progression of atherosclerosis.

No additional funding sources recorded.