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

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-up taken by parental brown adipocytes, mitochondria-derived EVs reduced peroxisome proliferator-activated receptor-g 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.

Automated summary

Recent findings show that mitochondria can be transferred between cells to control metabolic homeostasis. This study reveals that thermogenically stressed brown adipocytes release extracellular vesicles (EVs) containing damaged mitochondrial parts to avoid failure of the thermogenic program. The efficient removal of these EVs by tissue-resident macrophages is crucial for preserving the function of brown adipose tissue (BAT) and its response to cold exposure.