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Title

A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart

AuthorsNicolás-Ávila, José A.; Lechuga, Ana; Sanchez-Díaz, María; Díaz-García, Elena; Santiago, Demetrio J.; Rubio-Ponce, Andrea; LiangYao Li, Jackson; Balachander, Akhila; Quintana, Juan A.; Martínez de Mena, Raquel CSIC ORCID; Castejón-Vega, Beatriz; Pun-García, Andrés; Través, Paqui G.; Bonzón-Kulichenko, Elena CSIC ORCID; García-Marqués, Fernando; Cussó, Lorena; González, Noelia A.; González-Guerra, Andrés; Roche-Molina, Marta; Martin-Salamanca, Sandra; Crainiciuc, Georgiana; Guzmán, Gabriela; Larrazabal, Jagoba; Herrero-Galán, Elías; Alegre-Cebollada, Jorge; Lemke, Greg; Rothlin, Carla V.; Jiménez-Borreguero, Luis J.; Reyes, Guillermo; Castrillo, Antonio CSIC; Desco, Manuel; Muñoz-Cánoves, Pura; Ibáñez, Borja; Torres, Miguel; Guan Ng, Lai; Priori, Silvia G.; Bueno, Héctor; Vázquez, Jesús CSIC ORCID CVN; Cordero, Mario D. CSIC ORCID; Bernal, Juan CSIC ORCID; Enríquez, José Antonio; Hidalgo, Andrés
KeywordsMacrophage
Mitochondria
Autophagy
Proteostasis
Phagocytosis
Heart
Issue Date1-Oct-2020
PublisherElsevier
CitationCell 183(1): 94-109.e23 (2020)
AbstractCardiomyocytes 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: [Figure presented] A system of macrophages in the heart supports cardiomyocyte health by phagocytosing exopher particles ejected from cardiomyocytes that contain defective mitochondria, among other cellular contents.
Publisher version (URL)http://dx.doi.org/10.1016/j.cell.2020.08.031
URIhttp://hdl.handle.net/10261/226682
DOIhttp://dx.doi.org/10.1016/j.cell.2020.08.031
ISSN0092-8674
E-ISSN1097-4172
Appears in Collections:(IIBM) Artículos
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