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0123456789();: Mitochondrial transfer between cells has been previously demonstrated to control metabolic homeostasis. Whether mitochondrial transfer occurs in brown adipose tissue (BAT) and has a role in adaptive thermogenesis was unclear. A new study in Cell Metabolism now shows that brown adipocytes eject damaged mitochondria in extracellular vesicles (BAT-EVs), which are taken up by macrophages, thereby ensuring optimal thermogenesis. “Brown adipocytes have high metabolic activity and must cope with intense mitochondrial stress,” explains author Katia Aquilano. “Through high-throughput and functional analyses we discovered that brown adipocytes selectively sort and eject oxidatively damaged mitochondrial components into extracellular vesicles to assure mitochondrial efficiency under sustained metabolic activity.” This discovery was made using mouse primary brown adipocytes and a mouse brown adipocyte cell line. In addition, BAT-EVs from cold-exposed mice were enriched in proteins related to mitochondria and metabolism. Interestingly, treating brown adipocytes with BAT-EVs downregulated PPARγ signalling; a key pathway in brown adipocyte differentiation and thermogenesis. Furthermore, brown adipocytes treated with BAT-EVs also showed decreased levels of UCP1. Thus, BAT-EVs exert an autocrine effect that negatively regulates thermogenesis. Importantly, in vivo experiments in mice depleted of macrophages showed they had an abnormal accumulation of mitochondrial BAT-EVs and showed impaired thermogenesis upon cold exposure. These results suggest that BAT-resident macrophages take up damaged mitochondria contained within BAT-EVs to ensure proper BAT function. This study adds weight to the idea that mitochondrial trans fer between cells regulates metabolic homeostasis in adipose tissue. “A defective immune surveillance of macrophages, or even an impairment of the systems allowing the release of these debris into the extracellular environment, could be the basis of the onset of metabolic diseases, such as type 2 diabetes mellitus,” concludes author Daniele Lettieri-Barbato. “This topic merits further investigation, for example by studying the adipocyte-to-macrophage interaction via extracellular vesicles in experimental models of metabolic diseases.”