Efferocytosis and other corpse clearance transfers metal micronutrients to engulfing macrophages triggering a metallothionein response necessary to preserve mitochondrial function

Our study identifies metals as part of the corpse-derived metabolic load transferred to macrophages. We demonstrate a conserved role of macrophage metallothionein (MT) gene upregulation in the management of cell-derived metals transferred during engulfment of apoptotic corpses, necrotic corpses, or live cells. Mechanistically, MTs facilitate prompt control of free zinc released during corpse degradation in the phagolysosome.

MTs are necessary for macrophages to enhance oxidative phosphorylation in response to apoptotic cell engulfment, connecting control of corpse-derived metals to macrophage metabolic response. Collectively, these findings identify metals as micronutrients transferred from corpses to engulfing macrophages during efferocytosis and other corpse clearance and demonstrate an important role for metallothioneins in processing corpse-associated metals to preserve macrophage functions.