@article{39a22f5bcaa24b0a94809a2b032b2b34,
title = "Ejection of damaged mitochondria and their removal by macrophages ensure efficient thermogenesis in brown adipose tissue",
abstract = "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.",
keywords = "adipose tissue, brown adipocytes, extracellular vesicles, homeostasis, immunometabolism, macrophages, mitochondria, mitochondrial quality control, thermogenesis",
author = "Marco Rosina and Veronica Ceci and Riccardo Turchi and Li Chuan and Nicholas Borcherding and Francesca Sciarretta and Mar{\'i}a S{\'a}nchez-D{\'i}az and Flavia Tortolici and Keaton Karlinsey and Valerio Chiurchi{\`u} and Claudia Fuoco and Rocky Giwa and Field, {Rachael L.} and Matteo Audano and Simona Arena and Alessandro Palma and Federica Riccio and Farnaz Shamsi and Giovanni Renzone and Martina Verri and Anna Crescenzi and Salvatore Rizza and Fiorella Faienza and Giuseppe Filomeni and Sander Kooijman and Stefano Rufini and {de Vries}, {Antoine A.F.} and Andrea Scaloni and Nico Mitro and Tseng, {Yu Hua} and Andr{\'e}s Hidalgo and Beiyan Zhou and Brestoff, {Jonathan R.} and Katia Aquilano and Daniele Lettieri-Barbato",
note = "Funding Information: 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 , Universit{\`a} 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. Chiurchi{\`u}; 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 Innovaci{\'o}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 ). Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = apr,
day = "5",
doi = "10.1016/j.cmet.2022.02.016",
language = "English (US)",
volume = "34",
pages = "533--548.e12",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "4",
}