About Immunity

(9) Mitochondria and Macrophages

Mitochondria are organelles in cells. Their primary function is the production of adenosine triphosphate (ATP), which releases energy when it is hydrolyzed. The production of ATP by mitochondria is essential for the survival and functioning of cells. Therefore, it is vital to keep mitochondria fresh in the cells that consume a lot of energy, such as brain and heart cells.

Inside the cell, mitochondria that have lost their function are broken down and replaced by new ones. Recent research has shown that macrophages play an important role in the metabolism of mitochondria.

Nicolas-Avila et al. found that the loss of macrophages in the heart of mice decreased ventricular contractility and increased the number of abnormal mitochondria with reduced function in the myocardium (*1). Therefore, the absence of macrophages causes abnormalities in the mitochondria that supply energy to the heart.

When they investigated this mechanism, they found that old mitochondria in cardiomyocytes are recycled by autophagy (a mechanism used to break down proteins in the cell) or expelled from the cell. Additionally, the old mitochondria expelled from the cell are broken down by phagocytosis of macrophages. Therefore, in the absence of macrophages, old mitochondria discharged from the cell accumulate without being broken down.

Furthermore, as the extracellular accumulation of old mitochondria increases, autophagy within the cell is suppressed, decreasing the number of new, normal mitochondria. This decrease is associated with reduced ventricular contractility.

This study shows that macrophages regulate mitochondrial metabolism and energy supply.

（*1）A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart. Cell 183: 1-16 (2020)