A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart
| Autor: | Marta Roche-Molina, Jorge Alegre-Cebollada, Miguel Torres, Luis Jesús Jiménez-Borreguero, Akhila Balachander, Raquel Martínez-de-Mena, Greg Lemke, Andrés Hidalgo, Mario D. Cordero, Juan A. Bernal, Guillermo Reyes, José Ángel Nicolás-Ávila, Lai Guan Ng, Manuel Desco, Silvia G. Priori, Elena Díaz-García, Jackson LiangYao Li, Pura Muñoz-Cánoves, Lorena Cussó, Elena Bonzón-Kulichenko, Fernando García-Marqués, Demetrio J. Santiago, Georgiana Crainiciuc, Héctor Bueno, María Sánchez-Díaz, Carla V. Rothlin, Elías Herrero-Galán, Noelia A-Gonzalez, Lorena Esteban-Martínez, Borja Ibanez, Sandra Martín-Salamanca, Gabriela Guzmán, José Antonio Enríquez, Juan A. Quintana, Jesús Vázquez, Paqui G. Través, Jagoba Larrazabal, Andrés Pun-García, Antonio Castrillo, Ana Victoria Lechuga-Vieco, Andrés González-Guerra, Andrea Rubio-Ponce, Beatriz Castejón-Vega |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), European Research Council, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, Fondation Leducq, Comunidad de Madrid, La Caixa, Fundació La Marató de TV3, Fundación 'la Caixa', Howard Hughes Medical Institute, Centro Nacional de Investigaciones Cardiovasculares (España), Ministerio de Ciencia e Innovación (España), Fundación La Caixa, Comunidad de Madrid (España), Fundación La Marató TV3, Centro Nacional de Investigaciones Cardiovasculares Carlos III (España), Fundación ProCNIC |
| Rok vydání: | 2020 |
| Předmět: |
Male
Cell signaling Macrophage Myocardial Infarction Apoptosis Mitochondrion Biology General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences 0302 clinical medicine Phagocytosis medicine Autophagy Animals Homeostasis Humans Myocytes Cardiac Aged 030304 developmental biology 0303 health sciences c-Mer Tyrosine Kinase Macrophages Myocardium Receptor Protein-Tyrosine Kinases Inflammasome Heart Middle Aged MERTK 3. Good health Cell biology Mitochondria Mice Inbred C57BL Proteostasis Female Reactive Oxygen Species 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Cell |
| Popis: | 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. This study was supported by Intramural grants from the Severo Ochoa program (IGP-SO); grants SAF2015-71878-REDT and SAF2014-56819-R from the Ministerio de Ciencia e Innovacion (MICINN) to A.C.; European Research Council grant EU-rhythmy (ERC-ADG-2014-ID:669387) to S.G.P., and MATRIX (ERC-COG-2018-ID: 819775) to B.I.; L.G.N. is supported by SIgN core funding from A∗STAR; grant BFU2016-75144-R from the Ministry of Science and Innovation to J.A.B,; grants PGC2018-096486-B-I00 and RD16/0011/0019 (ISCIII) from MICINN, TNE-17CVD04 from the Leducq Foundation, and S2017/BMD-3875 from the Comunidad de Madrid to M.T; intramural grant TPC/O-SO and grants SAF2015-65633-R, RTI2018-099357-B-I00, and HFSP (RGP0016/2018) to J.A.E.; intramural grant IGP-SO to J.A.-C. and A.H.; BIO2017-83640-P and RYC-2014-16604 to J.A-C; grants PRB3 (IPT17/0019-ISCIII-SGEFI/ERDF, ProteoRed) from the Carlos III Institute of Health and Fondo de Investigaciones Sanitarias, BIO2015-67580-P and PGC2018-097019-B-I00 from MICINN to J.V.; RTI2018-096068 from MICINN, AFM, MDA, LaCaixa-HR17-00040, UPGRADE-H2020-825825, and European Research Council (ERC-741538) to P.M.C.; S2017/BMD-3867 RENIM-CM from the Comunidad de Madrid and cofunded with European structural and investment funds to M.D.; 120/C/2015-20153032 from Fundació la Marató de TV3, SAF2015-65607-R and RTI2018-095497-B-I00 from MICINN, HR17_00527 from La Caixa Foundation, and TNE-18CVD04 from the Leducq Foundation to A.H.; C.V.R. is a Howard Hughes Medical Institute Faculty Scholar; J.A.N-A is supported by fellowship SVP-2014-068595, A.V.L.-V. by SVP-2013-068089, L.E.-M. by FJCI-2016-29384, and A.R.-P. by BES-2016-076635, all from MICINN; and the CNIC International Postdoctoral Program (EU grant agreement 600396 to D.J.S.). The CNIC is supported by the MICINN and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MICINN award SEV-2015-0505). |
| Databáze: | OpenAIRE |
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