A network of macrophages supports mitochondrial homeostasis in the heart


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Cardiomyocytes are subjected to the intense mechanical stress and metabolic demands of the beating heart. It is unclear whether these cells, which are long-lived and rarely renew, manage to preserve homeostasis on their own. While analyzing macrophages lodged within the healthy myocardium, we discovered that they actively took up material, including mitochondria, derived from cardiomyocytes. Cardiomyocytes ejected dysfunctional mitochondria and other cargo in dedicated membranous particles reminiscent of neural exophers, through a process driven by the cardiomyocyte’s autophagy machinery that was enhanced during cardiac stress. Efficient uptake of these vesicles by macrophages through the receptor Mertk prevents extracellular accumulation of waste material, inflammasome activation, and autophagic block, altogether supporting heart homeostasis. Depletion of cardiac macrophages resulted in defective elimination of mitochondria from the myocardial tissue, metabolic alterations, and ventricular dysfunction. This immune-parenchymal pair in the murine heart enables transfer of unfit material to preserve metabolic stability and organ function.