TY - JOUR
T1 - Ejection of damaged mitochondria and their removal by macrophages ensure efficient thermogenesis in brown adipose tissue
AU - Rosina, Marco
AU - Ceci, Veronica
AU - Turchi, Riccardo
AU - Chuan, Li
AU - Borcherding, Nicholas
AU - Sciarretta, Francesca
AU - Sánchez-Díaz, María
AU - Tortolici, Flavia
AU - Karlinsey, Keaton
AU - Chiurchiù, Valerio
AU - Fuoco, Claudia
AU - Giwa, Rocky
AU - Field, Rachael L.
AU - Audano, Matteo
AU - Arena, Simona
AU - Palma, Alessandro
AU - Riccio, Federica
AU - Shamsi, Farnaz
AU - Renzone, Giovanni
AU - Verri, Martina
AU - Crescenzi, Anna
AU - Rizza, Salvatore
AU - Faienza, Fiorella
AU - Filomeni, Giuseppe
AU - Kooijman, Sander
AU - Rufini, Stefano
AU - de Vries, Antoine A.F.
AU - Scaloni, Andrea
AU - Mitro, Nico
AU - Tseng, Yu Hua
AU - Hidalgo, Andrés
AU - Zhou, Beiyan
AU - Brestoff, Jonathan R.
AU - Aquilano, Katia
AU - Lettieri-Barbato, Daniele
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/4/5
Y1 - 2022/4/5
N2 - 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.
AB - 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.
KW - adipose tissue
KW - brown adipocytes
KW - extracellular vesicles
KW - homeostasis
KW - immunometabolism
KW - macrophages
KW - mitochondria
KW - mitochondrial quality control
KW - thermogenesis
UR - http://www.scopus.com/inward/record.url?scp=85127363909&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2022.02.016
DO - 10.1016/j.cmet.2022.02.016
M3 - Article
C2 - 35305295
AN - SCOPUS:85127363909
SN - 1550-4131
VL - 34
SP - 533-548.e12
JO - Cell metabolism
JF - Cell metabolism
IS - 4
ER -