Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/11210
A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart.
Nicolas-Avila, Jose A. CNIC | Lechuga-Vieco, Ana V. CNIC | Esteban-Martinez, Lorena | Sanchez-Diaz, Maria CNIC | Díaz-García, Elena | Santiago, Demetrio J CNIC | Rubio-Ponce, Andrea CNIC | Li, Jackson LiangYao CNIC | Balachander, Akhila | Quintana, Juan A. CNIC | Martínez-de-Mena, Raquel | Castejón-Vega, Beatriz | Pun-Garcia, Andres CNIC | Través, Paqui G | Bonzon-Kulichenko, Elena CNIC | Garcia-Marques, Fernando CNIC | Cusso, Lorena CNIC | A-Gonzalez, Noelia CNIC | González-Guerra, Andrés | Roche-Molina, Marta CNIC | Martin-Salamanca, Sandra CNIC | Crainiciuc, Georgiana CNIC | Guzman-Martinez, Gabriela CNIC | Larrazabal, Jagoba | Herrero-Galán, Elías CNIC | Alegre-Cebollada, Jorge CNIC | Lemke, Greg | Rothlin, Carla V | Jimenez-Borreguero, Luis J. CNIC | Reyes, Guillermo | Castrillo, Antonio | Desco, Manuel CNIC | Munoz-Canoves, Pura CNIC | Ibanez, Borja CNIC | Torres, Miguel CNIC | Ng, Lai Guan | Priori, Silvia G. CNIC | Bueno, Héctor CNIC | Vazquez, Jesus CNIC | Cordero, Mario D | Bernal, Juan Antonio CNIC | Enriquez, José Antonio CNIC | Hidalgo, Andrés CNIC
Cell. 2020; 183(1):94-109
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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