Ejection of damaged mitochondria and their removal by macrophages ensure efficient thermogenesis in brown adipose tissue
| Autor: | Marco Rosina, Veronica Ceci, Riccardo Turchi, Chuan Li, Nicholas Borcherding, Francesca Sciarretta, María Sánchez-Díaz, Flavia Tortolici, Keaton Karlinsey, Valerio Chiurchiù, Claudia Fuoco, Rocky Giwa, Rachael L. Field, Matteo Audano, Simona Arena, Alessandro Palma, Federica Riccio, Farnaz Shamsi, Giovanni Renzone, Martina Verri, Anna Crescenzi, Salvatore Rizza, Fiorella Faienza, Giuseppe Filomeni, Sander Kooijman, Stefano Rufini, Antoine A.F. de Vries, Andrea Scaloni, Nico Mitro, Yu-Hua Tseng, Andrés Hidalgo, Beiyan Zhou, Jonathan R. Brestoff, Katia Aquilano, Daniele Lettieri-Barbato |
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| Přispěvatelé: | European Foundation for the Study of Diabetes, Boehringer Ingelheim Fonds, Fondation Leducq, Ministerio de Ciencia e Innovación (España), Fundación La Caixa |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
brown adipocytes
thermogenesis Physiology mitochondrial quality control Macrophages immunometabolism Thermogenesis Cell Biology Settore BIO/09 Mitochondria adipose tissue macrophages mitochondria Adipocytes Brown Adipose Tissue Brown homeostasis Settore BIO/10 extracellular vesicles Molecular Biology Uncoupling Protein 1 |
| Zdroj: | Cell metabolism 34 (2022): 533–548. doi:10.1016/j.cmet.2022.02.016 info:cnr-pdr/source/autori:Marco Rosina, Veronica Ceci, Riccardo Turchi, Li Chuan, Nicholas Borcherding, Francesca Sciarretta, María Sánchez-Díaz, Flavia Tortolici, Keaton Karlinsey, Valerio Chiurchiù, Claudia Fuoco, Rocky Giwa, Rachael L Field, Matteo Audano, Simona Arena, Alessandro Palma, Federica Riccio, Farnaz Shamsi, Giovanni Renzone, Martina Verri, Anna Crescenzi, Salvatore Rizza, Fiorella Faienza, Giuseppe Filomeni, Sander Kooijman, Stefano Rufini, Antoine A F de Vries, Andrea Scaloni, Nico Mitro, Yu-Hua Tseng, Andrés Hidalgo, Beiyan Zhou, Jonathan R Brestoff, Katia Aquilano, Daniele Lettieri-Barbato/titolo:Ejection of damaged mitochondria and their removal by macrophages ensure efficient thermogenesis in brown adipose tissue/doi:10.1016%2Fj.cmet.2022.02.016/rivista:Cell metabolism/anno:2022/pagina_da:533/pagina_a:548/intervallo_pagine:533–548/volume:34 Cell Metabolism, 34(4), 533-548.e12. CELL PRESS |
| DOI: | 10.1016/j.cmet.2022.02.016 |
| Popis: | Recent findings have demonstrated that mitochondria can be transferred between cells to control metabolic homeostasis. Although the mitochondria of brown adipocytes comprise a large component of the cell volume and undergo reorganization to sustain thermogenesis, it remains unclear whether an intercellular mitochondrial transfer occurs in brown adipose tissue (BAT) and regulates adaptive thermogenesis. Herein, we demonstrated that thermogenically stressed brown adipocytes release extracellular vesicles (EVs) that contain oxidatively damaged mitochondrial parts to avoid failure of the thermogenic program. When re-uptaken by parental brown adipocytes, mitochondria-derived EVs reduced peroxisome proliferator-activated receptor-γ signaling and the levels of mitochondrial proteins, including UCP1. Their removal via the phagocytic activity of BAT-resident macrophages is instrumental in preserving BAT physiology. Depletion of macrophages in vivo causes the abnormal accumulation of extracellular mitochondrial vesicles in BAT, impairing the thermogenic response to cold exposure. These findings reveal a homeostatic role of tissue-resident macrophages in the mitochondrial quality control of BAT. This work was partially supported by the European Foundation for the Study of Diabetes (EFSD/Lilly, 2017 and EFSD/Boehringer Ingelheim European Research Programme on ‘‘Multi-System Challenges in Diabetes’’) and the Italian Ministry of Health (GR-2018-12367588) to D.L.-B.; Associazione Italiana per la Ricerca sul Cancro (AIRC) under IG 2019 - ID. 23562 project to K.A.; MIUR ‘‘Progetto Eccellenza’’ to Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita` degli Studi di Milano, and NUTRAGE (CNR FOE 2019, DSB.AD004.271) to A.S; Italian Foundation of Multiple Sclerosis (grant 2017/R/8), the Italian Ministry of Health (grant GR-2016-02362380) and the MAI Award grant to V. Chiurchiu; National Institutes of Health (NIH) common fund (DP5 OD028125) and the Burroughs Wellcome Fund (1019648) to J.R.B.; NIH K01DK125608 to F.S.; R01DK102898 and R01DK122808 to Y.- H.T.; and NIH RO1 DK121805 and AHA 19TPA34910079 to B.Z. A.H. was supported by RTI2018-095497-B-I00 from MICINN, HR17_00527 from La Caixa Foundation, and TNE-18CVD04 from the Leducq Foundation. M.S-D was supported by a fellowship PRE2019-08746 from the Ministerio de Ciencia e Innovacio´ n. M.R. was partially supported by a fellowship from AIRC (IG 2019 - ID. 23562) and by the Italian Ministry of Health (SG-2019-12368589). V.C. is part of the PhD Program in Evolutionary Biology and Ecology, Department of Biology, University of Rome Tor Vergata. Sí |
| Databáze: | OpenAIRE |
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