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Publication : A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart.

First Author  Nicolás-Ávila JA Year  2020
Journal  Cell Volume  183
Issue  1 Pages  94-109.e23
PubMed ID  32937105 Mgi Jnum  J:296900
Mgi Id  MGI:6460205 Doi  10.1016/j.cell.2020.08.031
Citation  Nicolas-Avila JA, et al. (2020) A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart. Cell 183(1):94-109.e23
abstractText  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. Depletion of cardiac macrophages or deficiency in the phagocytic receptor Mertk resulted in defective elimination of mitochondria from the myocardial tissue, activation of the inflammasome, impaired autophagy, accumulation of anomalous mitochondria in cardiomyocytes, metabolic alterations, and ventricular dysfunction. Thus, we identify an immune-parenchymal pair in the murine heart that enables transfer of unfit material to preserve metabolic stability and organ function. VIDEO ABSTRACT.
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