A network of macrophages supports mitochondrial homeostasis in the heart Articles uri icon

authors

  • Nicolás-Ávila, Ávila, José Ángel
  • Lechuga Vieco, Ana Victoria
  • Esteban Martínez, Lorena
  • Sánchez Díaz, María
  • Díaz García, Elena
  • Santiago, Demetrio J.
  • Rubio Ponce, Andrea
  • Li, Jackson Liangyao
  • Balachander, Akhila
  • Quintana, Juan Antonio
  • Martínez de Mena, Raquel
  • Castejón Vega, Beatriz
  • Pun García, Andrés
  • Través, Paqui G.
  • Bonzón Kulichenko, Elena
  • García Marqués,, Fernando Jose
  • CUSSO MULA, LORENA
  • A-Gonzalez, Noelia
  • González Guerra, Andrés
  • Roche Molina, Marta
  • Martín Salamanca, Sandra
  • Crainiciuc, Georgiana
  • Guzmán, Gabriela
  • Larrazabal, Jagoba
  • Herrero Galán, Elías
  • Alegre Cebollada, Jorge
  • Lemke, Greg E.
  • Rothlin, Carla Vanina
  • Jiménez Borreguero, L.
  • Reyes, Guillermo
  • Castrillo, Antonio
  • DESCO MENENDEZ, MANUEL
  • Muñoz Cánoves, Pura
  • IBAÑEZ, BORJA
  • Torres, Miguel S.
  • Ng, Lai Guan
  • Priori, Silvia G.
  • Bueno, Héctor
  • Vázquez, Jesús
  • Cordero, Mario David
  • Bernal, Juan A.
  • Enríquez, José Antonio
  • Hidalgo, Andrés

published in

publication date

  • October 2020

start page

  • 94

end page

  • 109

issue

  • 1

volume

  • 183

International Standard Serial Number (ISSN)

  • 0092-8674

abstract

  • 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: [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. © 2020 Elsevier Inc.

keywords

  • aged; animals; apoptosis; autophagy; c-mer tyrosine kinase; female; heart; homeostasis; humans; macrophages; male; mice; inbred c57bl; middle aged; mitochondria; myocardial infarction; myocardium; myocytes, cardiac; phagocytosis; reactive oxygen species; receptor protein-tyrosine kinases; inflammasome; protein kinase mer; protein kinase mer; protein tyrosine kinase; reactive oxygen metabolite; adult; animal cell; animal experiment; animal model; animal tissue; article; autophagy (cellular); cardiac muscle cell; cell component; cell metabolism; clearance; controlled study; depletion; exopher; heart mitochondrion; heart stress; heart ventricle function; homeostasis; human; human tissue; infant; macrophage; male; metabolic stability; mouse; nonhuman; phagocytosis; priority journal; aged; animal; apoptosis; autophagy; c57bl mouse; cardiac muscle; cardiac muscle cell; female; heart; heart infarction; homeostasis; macrophage; metabolism; middle aged; mitochondrion; physiology