LAUSR

Defective efferocytosis, the process of apoptotic cell clearance by macrophages, is a critical factor in the pathogenesis of atherosclerosis that leads to the accumulation of apoptotic cells and debris in atherosclerotic plaques. Uptake of multiple apoptotic cells by individual phagocytes is essential for the proper functioning of efferocytosis. Wang et al. now provide new insights into this process by showing that mitochondrial fission is required for continued efferocytosis. Apoptotic cell uptake by macrophages triggers mitochondrial fission induced by dynamin-related protein 1 (DRP1). Mitochondrial fission then enables efficient apoptotic cell degradation in phagolysosomes, as well as release of Ca from the endoplasmic reticulum into the cytoplasm and Ca-mediated vesicular trafficking, which in turn enable phagocytosis of a second apoptotic cell. Mice lacking DRP1 in myeloid cells have defective efferocytosis, which promotes the formation of advanced atherosclerotic lesions in Ldlr mice fed a high-fat diet.