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

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 VerriAnna 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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)533-548.e12
JournalCell Metabolism
Issue number4
StatePublished - Apr 5 2022


  • adipose tissue
  • brown adipocytes
  • extracellular vesicles
  • homeostasis
  • immunometabolism
  • macrophages
  • mitochondria
  • mitochondrial quality control
  • thermogenesis

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


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