Ejection of damaged mitochondria and their removal by macrophages ensure efficient thermogenesis in brown adipose tissue.

Autor:	Rosina M; Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy; Neurology Unit, Fondazione PTV Policlinico Tor Vergata, Viale Oxford 81, 00133 Rome, Italy., Ceci V; Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy., Turchi R; Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy., Chuan L; Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT 06030, USA., Borcherding N; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Sciarretta F; IRCCS, Fondazione Santa Lucia, 00179 Rome, Italy., Sánchez-Díaz M; Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain., Tortolici F; Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy., Karlinsey K; Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT 06030, USA., Chiurchiù V; IRCCS, Fondazione Santa Lucia, 00179 Rome, Italy; Institute of Translational Pharmacology, Laboratory of Resolution of Neuroinflammation, National Research Council, 00133 Rome, Italy., Fuoco C; Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy., Giwa R; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Field RL; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Audano M; Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy., Arena S; Proteomics, Metabolomics and Mass Spectrometry Laboratory, ISPAAM-National Research Council, Portici, 80055 Naples, Italy., Palma A; Department of Onco-Hematology, Gene and Cell Therapy, Bambino Gesù Children's Hospital IRCCS, 00146 Rome, Italy., Riccio F; Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy., Shamsi F; Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010, USA., Renzone G; Proteomics, Metabolomics and Mass Spectrometry Laboratory, ISPAAM-National Research Council, Portici, 80055 Naples, Italy., Verri M; Pathology Unit, University Hospital Campus Bio-Medico of Rome, 00128 Rome, Italy., Crescenzi A; Pathology Unit, University Hospital Campus Bio-Medico of Rome, 00128 Rome, Italy., Rizza S; Danish Cancer Society Research Center, 2100 Copenhagen, Denmark., Faienza F; Danish Cancer Society Research Center, 2100 Copenhagen, Denmark., Filomeni G; Danish Cancer Society Research Center, 2100 Copenhagen, Denmark., Kooijman S; Department of Medicine, Division of Endocrinology, and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands., Rufini S; Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy., de Vries AAF; Department of Cardiology, Laboratory of Experimental Cardiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands., Scaloni A; Proteomics, Metabolomics and Mass Spectrometry Laboratory, ISPAAM-National Research Council, Portici, 80055 Naples, Italy., Mitro N; Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133 Milan, Italy., Tseng YH; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA., Hidalgo A; Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain., Zhou B; Department of Immunology, School of Medicine, University of Connecticut, Farmington, CT 06030, USA; Institute for Systems Genomics, University of Connecticut, Farmington, CT 06030, USA., Brestoff JR; Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA., Aquilano K; Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy. Electronic address: katia.aquilano@uniroma2.it., Lettieri-Barbato D; Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy; IRCCS, Fondazione Santa Lucia, 00179 Rome, Italy. Electronic address: daniele.lettieri.barbato@uniroma2.it.
Jazyk:	angličtina
Zdroj:	Cell metabolism [Cell Metab] 2022 Apr 05; Vol. 34 (4), pp. 533-548.e12. Date of Electronic Publication: 2022 Mar 18.
DOI:	10.1016/j.cmet.2022.02.016
Abstrakt:	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. Competing Interests: Declaration of interests J.R.B. has a pending patent application related to mitochondria transfer. The other authors declare no competing interests. (Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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