A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart
Creators
- Nicolás-Ávila, José Ángel1
- Lechuga-Vieco, Ana Victoria2
- Esteban-Martínez, Lorena1
- Sánchez-Díaz, María1
- Díaz-García, Elena1
- Santiago, Demetrio J.1
- Rubio-Ponce, Andrea1
- LiangYao Li, Jackson1
- Balachander, Akhila3
- Quintana, Juan A.1
- Martínez-de-Mena, Raquel3
- Castejón-Vega, Beatriz4
- Pun-García, Andrés1
- Través, Paqui G5
- Bonzón-Kulichenko, Elena6
- García-Marqués, Fernando1
- Cussó, Lorena7
- A-Gonzalez, Noelia8
- González-Guerra, Andrés1
- Roche-Molina, Marta1
- Martín-Salamanca, Sandra1
- Crainiciuc, Georgiana1
- Guzmán, Gabriela9
- Larrazabal, Jagoba1
- Herrero-Galán, Elías1
- Alegre-Cebollada, Jorge1
- Lemke, Greg5
- Rothlin, Carla V.10
- Jiménez-Borreguero, Luis Jesús11
- Reyes, Guillermo12
- Castrillo, Antonio13
- Desco, Manuel14
- Muñoz-Cánoves, Pura15
- Ibanez, Borja16
- Torres, Miguel1
- Guan Ng, Lai3
- Priori, Silvia G.17
- Bueno, Héctor6
- Vázquez, Jesús6
- Cordero, Mario D.18
- Bernal, Juan A.1
- Enríquez, José Antonio19
- Hidalgo, Andrés1
- 1. Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain
- 2. Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain - CIBER de enfermedades respiratorias (CIBERES), Madrid 28029, Spain
- 3. Singapore Immunology Nework (SIgN), A∗STAR, Biopolis, Singapore 138648, Singapore
- 4. Oral Medicine Department, University of Sevilla, Seville 41009, Spain
- 5. Molecular Neurobiology Laboratory, the Salk Institute for Biological Studies, La Jolla, CA 92037, USA
- 6. Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain - CIBER de enfermedades cardiovasculares (CIBERCV), Madrid 28029, Spain
- 7. Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain - Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid 28911, Spain - Instituto de Investigación Sanitaria Gregorio Marañón, Madrid 28009, Spain - Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid 28029, Spain
- 8. Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain - Institute of Immunology, University of Muenster, Muenster 48149, Germany
- 9. Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain - Hospital Universitario La Paz, IdIPaz, Madrid 28046, Spain
- 10. Departments of Immunobiology and Pharmacology, Yale University, New Haven, CT 06520, USA
- 11. CIBER de enfermedades cardiovasculares (CIBERCV), Madrid 28029, Spain - Hospital Universitario de La Princesa, Madrid 28006, Spain
- 12. Hospital Universitario de La Princesa, Madrid 28006, Spain
- 13. Instituto Investigaciones Biomédicas "Alberto Sols," CSIC-UAM, Madrid 28029, Spain - Unidad de Biomedicina IIBM-Universidad de las Palmas de Gran Canaria (ULPGC) (Unidad Asociada al CSIC), Las Palmas 35001, Spain - Instituto Universitario de Investigaciónes Biomédicas y Sanitarias, ULPGC, Las Palmas 35016, Spain
- 14. Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain - Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid 28911, Spain
- 15. Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain - Department of Experimental & Health Sciences, Universitat Pompeu Fabra, CIBERNED, Barcelona 08003, Spain - ICREA, Barcelona 08908, Spain
- 16. Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain - CIBER de enfermedades cardiovasculares (CIBERCV), Madrid 28029, Spain - IS- Fundación Jiménez Díaz Hospital, Madrid 28040, Spain
- 17. Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain - Molecular Cardiology, ICS-Maugeri IRCCS, Pavia 27100, Italy - Department of Molecular Medicine, University of Pavia, Pavia 2700, Italy
- 18. Oral Medicine Department, University of Sevilla, Seville 41009, Spain - Cátedra de Reproducción y Genética Humana del Instituto para el Estudio de la Biología de la Reproducción Humana (INEBIR) y la Universidad Europea del Atlántico (UNEATLANTICO), Seville 41009, Spain - Fundación Universitaria Iberoamericana (FUNIBER), Barcelona 08005, Spain
- 19. Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain - CIBER de fragilidad y envejecimiento saludable (CIBERFES), Madrid 28029, Spain
Description
Summary
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.
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Nicolas-Avila et al 2020.pdf
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